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MAG111539: Safety Escalating Repeat IV, in Stroke Patients

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT00833989
Collaborator
(none)
42
Enrollment
15
Locations
2
Arms
18.8
Actual Duration (Months)
2.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to is to test increasing repeat doses of GSK249320 compared to placebo in patients with stroke.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Other
Official Title:
A Single-Blind Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Repeat Doses of GSK249320 in Patients With Stroke
Actual Study Start Date :
Jul 8, 2009
Actual Primary Completion Date :
Jan 31, 2011
Actual Study Completion Date :
Jan 31, 2011

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: PLACEBO

Drug: PLACEBO
Placebo
Experimental: ACTIVE

Drug: GSK249320
I.V. infusion

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) [Up to 112 days]

    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.

  2. Number of Participants With Vital Signs Changes of Potential Clinical Importance [Up to 112 days]

    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.

  3. Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance [Up to 112 days]

    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.

  4. Number of Participants With Nerve Conduction Testing (NCT) Values [Day 5 and 30 and at early withdrawal]

    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.

  5. Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) [Up to Day 60]

    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.

  6. Number of Participants With Abnormal Clinical Chemistry Parameters [Up to Day 112]

    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.

  7. Number of Participants With Abnormal Hematological Parameters [Up to Day 112]

    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.

Secondary Outcome Measures

  1. Number of Participants With Positive Antibodies to GSK249320 [Day 1, 5, 10, 30, 60, 90 and 112]

    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.

  2. 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) [Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)]

    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.

  3. Mean Maximum Observed Concentration (Cmax) and Last Observed Quantifiable Concentration (Ct) [Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)]

    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.

  4. Mean Time of Occurrence of Cmax (Tmax) and Time of Last Observed Quantifiable Concentration (Tlast) [Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)]

    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.

  5. Mean Terminal Phase Half-life (t1/2) [Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)]

    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.

  6. Mean Terminal Phase Rate Constant ( Lambda-Z) [Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)]

    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.

  7. Mean Clearance of GSK249320 [Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)]

    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).

  8. Mean Change in Mean Gait Velocity [Baseline (Day 5), Day 30, 60, 90, 112]

    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.

  9. Mean Change in Berg Balance Scale (BBS) Total Score [Baseline (Day 5), Day 30, 60, 90 and 112]

    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.

  10. Mean Change in Total Fugl-Meyer Motor (FM) Assessment [Baseline (Day 5), Day 30 and 112]

    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.

  11. Mean Change in Total Box and Blocks Transferred on Affected Side [Baseline (Day 1), Day 30, 60, 90 and 112]

    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.

  12. Mean Change in Grip Strength on Affected Side [Baseline (Day 1), Day 30, 60, 90 and 112]

    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.

  13. Number of Participants With Modified Rankin Scale (mRS) [Day 30 and 90]

    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.

  14. Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) [Baseline (Day 1), Day 10, 30 and 90]

    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.

  15. Mean Barthel Total Score [Day 30 and 90]

    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.

  16. Mean Total Montreal Cognitive Assessment (MoCA) Score [Day 5 and 90]

    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.

  17. Mean Geriatric Depression Scale (GDS) [Day 5 and 90]

    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.

  18. Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level [Baseline (Day 1), Day 30 and 112]

    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.

  19. Serum Levels of the S100β Protein [Day 1 (Pre-dose, Post dose 1, 6, 24 hour), Day 5]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 90 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Have a confirmed diagnosis of stroke

  • Stroke onset must be within the last 24-72 hours.

  • Have a stroke that is either:

  • radiologically confirmed to be ischaemic and supratentorial. The diameter of the ischemic lesion is >15mm in any singlle direction or the volume is >4cc. OR

  • radiologically confirmed to be an intracerebral hemorrhage that is supratentorial, deep (i.e., blood must not directly contact cerebral cortex) and with minimal or no intraventricular extension. The Intracerebral Hemorrahage (CH) score must be 0-2 and is calculated based on age, Galsgow coma Scale score ad the initial CT or MRI findings for the index stroke. See the SOM for the full calculation procedure.

  • Have a total NIHSS score of 3-21.

  • Have an upper and/or lower limb deficit defined as:

  • Score of 1-3 on the NIHSS Motor Arm question, and palpable and observable voluntary extension or flexion of the fingers. AND/OR b. Score of 1-3 on the NIHSS Motor Leg question

  • Aged 18-90, inclusive.

  • Male subjects and females of non-child-bearing potential are allowed to participate in this study.

  • Females of child-bearing potential are also allowed to participate in this study provided they are using a contraceptive method with a failure rate of <1%.

Exclusion Criteria:

  • History of a previous symptomatic stroke within 3 months prior to study entry.

  • Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke Rankin score of >2.

  • Presence of depression that is active and not adequately controlled such that it interferred with major activities of daily living immediately prior to the current stroke.

  • Subjects who are not alert or are unresponsive as defined by a score of 2 or 3 on the NIHSS Level of Consciousness question (question #1a).

  • Presence of significant aphasia as likely to confound or interfere with completion of the study assessments.

  • Presence of peripheral neuropathy, including diabetic neuropathy, which is clinically active and symptomatic at time of screening.

  • Presence of neurological or psychiatric disease, such as dementia or mild cognitive impairment, prior to study entry that is likely to confound clinical evaluations.

  • Presence of a demyelinating disease, such as multiple sclerosis.

  • Evidence of other chronic co-morbid conditions or unstable acute systemic illnesses which, in the opinion of the investigator, could shorten the subject's survival or limit his/her ability to complete the study.

  • History of sensitivity to heparin or heparin-induced thrombocytopenia.

  • Presence of QTcB > 500 msec; or uncorrected QT >600msec (machine or manual over-read) on baseline ECG.

  • Contraindication to TMS, such as:

  • have metal present, such as hardware or plate on the scalp in the area to which TMS will be applied, implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials

  • occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan.

  • concomitant use of drugs that substantially lower seizure threshold (e.g., tricyclic antidepressants and neuroleptics)

  • known history of seizures or epilepsy

  • brain tumor, recent brain injury (within 5 years) associated with definite loss of consciousness, or any history of brain surgery

  • Contraindication to MRI, such as:

  • have metal present, such as implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials, permanent tattooed metallic eye-liner

  • occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan.

  • claustrophobia

  • Participation in any investigational rehabilitation paradigm targeting stroke recovery during the duration of this study.

  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

Pregnant or lactating females.

  • Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Los Angeles California United States 90095-6984
2 GSK Investigational Site Orange California United States 92868-4280
3 GSK Investigational Site Fort Collins Colorado United States 80524
4 GSK Investigational Site Detroit Michigan United States 48201
5 GSK Investigational Site Portland Oregon United States 97239
6 GSK Investigational Site Toronto Ontario Canada M4N 3M5
7 GSK Investigational Site Montreal Quebec Canada H3T 1E2
8 GSK Investigational Site Ulm Baden-Wuerttemberg Germany 89081
9 GSK Investigational Site Wiesbaden Hessen Germany 65199
10 GSK Investigational Site Celle Niedersachsen Germany 29223
11 GSK Investigational Site Hannover Niedersachsen Germany 30625
12 GSK Investigational Site Essen Nordrhein-Westfalen Germany 45122
13 GSK Investigational Site Koeln Nordrhein-Westfalen Germany 50937
14 GSK Investigational Site Mainz Rheinland-Pfalz Germany 55131
15 GSK Investigational Site Leipzig Sachsen Germany 04103

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00833989
Other Study ID Numbers:
  • 111539
First Posted:
Feb 2, 2009
Last Update Posted:
Nov 17, 2017
Last Verified:
Sep 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Ischemic Attack, Transient

Study Results

Participant Flow

Recruitment Details 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.
Pre-assignment Detail A total of 42 participants were randomized and included in All subject population.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Period Title: Overall Study
STARTED 17 8 9 8
COMPLETED 14 8 8 6
NOT COMPLETED 3 0 1 2

Baseline Characteristics

Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg Total
Arm/Group Description 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. 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. 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. 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 Total of all reporting groups
Overall Participants 17 8 9 8 42
Age (Year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Year]
67.6
(10.79)
62.1
(13.01)
63.9
(13.76)
59.3
(12.99)
64.2
(12.27)
Sex: Female, Male (Count of Participants)
Female
11
64.7%
3
37.5%
5
55.6%
4
50%
23
54.8%
Male
6
35.3%
5
62.5%
4
44.4%
4
50%
19
45.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
1
12.5%
0
0%
1
12.5%
2
4.8%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
0
0%
0
0%
0
0%
White
17
100%
7
87.5%
9
100%
7
87.5%
40
95.2%
More than one race
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
00
0%
0
0%
0
0%
0
0%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Description 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.
Time Frame Up to 112 days

Outcome Measure Data

Analysis Population Description
All Subjects population was defined as all participants who receive at least one dose of study medication.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Any AE
11
64.7%
6
75%
8
88.9%
6
75%
Any SAE
3
17.6%
1
12.5%
3
33.3%
3
37.5%
2. Primary Outcome
Title Number of Participants With Vital Signs Changes of Potential Clinical Importance
Description 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.
Time Frame Up to 112 days

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
SBP, Visit 1, Day 1, 30 minute, High
1
5.9%
0
0%
0
0%
0
0%
SBP, Visit 1, Day 1, 1 hour, High
1
5.9%
0
0%
0
0%
0
0%
SBP, Visit 1, Day 1, 1 hour, Low
1
5.9%
0
0%
0
0%
0
0%
SBP, Visit 1, Day 1, 2 hour, High
2
11.8%
0
0%
0
0%
0
0%
SBP, Visit 1, Day 1, 4 hour, High
1
5.9%
0
0%
0
0%
1
12.5%
SBP, Visit 1, Day 1, 8 hour, High
1
5.9%
0
0%
0
0%
0
0%
SBP, Visit 1, Day 1, 12 hour, High
0
0%
1
12.5%
0
0%
1
12.5%
SBP, Visit 1, Day 1, 12 hour, Low
0
0%
0
0%
1
11.1%
0
0%
SBP, Visit 1, Day 1, 24 hour, High
0
0%
0
0%
1
11.1%
0
0%
SBP, Visit 6, Day 90, Low
0
0%
0
0%
1
11.1%
0
0%
SBP, Visit 7, Day 112, Low
1
5.9%
0
0%
0
0%
0
0%
DBP, Visit 1, Day 1, 15 minute, Low
0
0%
0
0%
1
11.1%
0
0%
DBP, Visit 1, Day 1, 1 hour, High
1
5.9%
0
0%
0
0%
0
0%
DBP, Visit 1, Day 1, 2 hour, High
1
5.9%
0
0%
0
0%
0
0%
DBP, Visit 1, Day 1, 2 hour, Low
0
0%
1
12.5%
0
0%
0
0%
DBP, Visit 1, Day 1, 4 hour, High
0
0%
1
12.5%
0
0%
0
0%
DBP, Visit 1, Day 1, 12 hour, High
1
5.9%
0
0%
0
0%
0
0%
DBP, Visit 2, Day 5, High
0
0%
0
0%
1
11.1%
0
0%
DBP, Visit 3, Day 10, 30 minute, High
1
5.9%
0
0%
0
0%
0
0%
HR, Visit 1, Day 1, 0 hour, High
0
0%
1
12.5%
0
0%
0
0%
HR, Visit 1, Day 1, 15 minute, High
0
0%
1
12.5%
0
0%
0
0%
HR, Visit 1, Day 1, 30 minute, High
1
5.9%
1
12.5%
0
0%
0
0%
HR, Visit 1, Day 1, 45 minute, High
1
5.9%
1
12.5%
1
11.1%
0
0%
HR, Visit 1, Day 1, 1 hour, High
0
0%
1
12.5%
0
0%
0
0%
HR, Visit 1, Day 1, 2 hour, High
0
0%
1
12.5%
1
11.1%
0
0%
HR, Visit 1, Day 1, 12 hour, High
0
0%
0
0%
1
11.1%
0
0%
HR, Visit 1, Day 1, 24 hour, High
0
0%
0
0%
0
0%
1
12.5%
HR, Visit 2, Day 5, High
0
0%
0
0%
1
11.1%
0
0%
HR, Visit 3, Day 10, 0 hour, High
1
5.9%
1
12.5%
0
0%
0
0%
HR, Visit 3, Day 10, 15 minute, High
0
0%
1
12.5%
0
0%
0
0%
HR, Visit 3, Day 10, 30 minute, High
1
5.9%
1
12.5%
0
0%
0
0%
HR, Visit 3, Day 10, 45 minute, High
1
5.9%
1
12.5%
0
0%
0
0%
HR, Visit 3, Day 10, 1 hour, High
1
5.9%
0
0%
0
0%
0
0%
HR, Visit 3, Day 10, 3 hour, High
1
5.9%
0
0%
0
0%
0
0%
HR, Visit 4, Day 30, High
0
0%
1
12.5%
0
0%
0
0%
3. Primary Outcome
Title Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance
Description 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.
Time Frame Up to 112 days

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 1, Day 1, Predose
2
11.8%
1
12.5%
1
11.1%
0
0%
Visit 1, Day 1, 24 hour
2
11.8%
1
12.5%
1
11.1%
0
0%
Visit 2, Day 5
2
11.8%
0
0%
0
0%
0
0%
Visit 3, Day 10, Predose
2
11.8%
0
0%
1
11.1%
0
0%
Visit 3, Day 10, 3 hour
2
11.8%
1
12.5%
1
11.1%
0
0%
Visit 4, Day 30
1
5.9%
1
12.5%
1
11.1%
0
0%
Visit 5, Day 60
1
5.9%
0
0%
1
11.1%
0
0%
Visit 6, Day 90
1
5.9%
0
0%
0
0%
0
0%
Visit 7, Day 112
1
5.9%
0
0%
0
0%
0
0%
4. Primary Outcome
Title Number of Participants With Nerve Conduction Testing (NCT) Values
Description 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.
Time Frame Day 5 and 30 and at early withdrawal

Outcome Measure Data

Analysis Population Description
All Subject population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Motor, Visit 2, Day 5, Normal
11
64.7%
7
87.5%
7
77.8%
4
50%
Motor, Visit 2, Day 5, Abnormal, secondary to
4
23.5%
1
12.5%
2
22.2%
4
50%
Motor, Visit 4, Day 30, Normal
11
64.7%
7
87.5%
6
66.7%
4
50%
Motor, Visit 4, Day 30, Abnormal, secondary to
3
17.6%
1
12.5%
2
22.2%
3
37.5%
Motor, Early Withdrawal, Abnormal, secondary to
2
11.8%
0
0%
0
0%
0
0%
Sensory, Visit 2, Day 5, Normal
9
52.9%
4
50%
6
66.7%
3
37.5%
Sensory, Visit 2, Day 5, Abnormal, secondary to
5
29.4%
4
50%
3
33.3%
5
62.5%
Sensory, Not done
1
5.9%
0
0%
0
0%
0
0%
Sensory, Visit 4, Day 30, Normal
12
70.6%
5
62.5%
7
77.8%
3
37.5%
Sensory, Visit 4, Day 30, Abnormal, secondary to
2
11.8%
3
37.5%
1
11.1%
4
50%
Sensory, Early Withdrawal, Normal,
1
5.9%
0
0%
0
0%
0
0%
Sensory, Early Withdrawal, Abnormal, secondary to
1
5.9%
0
0%
0
0%
0
0%
5. Primary Outcome
Title Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI)
Description 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.
Time Frame Up to Day 60

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
White matter change, Day 10 compared to Day 1
9
52.9%
5
62.5%
5
55.6%
2
25%
White matter change, Day 60 compared to Day 1
6
35.3%
6
75%
2
22.2%
3
37.5%
White matter change, Day 60 compared to Day 10
5
29.4%
5
62.5%
1
11.1%
3
37.5%
Demyelination, Day 10 compared to Day 1, Yes
1
5.9%
0
0%
3
33.3%
0
0%
Demyelination, Day 10 compared to Day 1, No
13
76.5%
8
100%
6
66.7%
7
87.5%
Demyelination, Day 60 compared to Day 1, No
14
82.4%
8
100%
9
100%
6
75%
Demyelination, Day 60 compared to Day 10, No
14
82.4%
8
100%
9
100%
6
75%
Demyelination, During Study, Yes
2
11.8%
0
0%
3
33.3%
0
0%
Demyelination, During Study, No
13
76.5%
8
100%
6
66.7%
7
87.5%
6. Primary Outcome
Title Number of Participants With Abnormal Clinical Chemistry Parameters
Description 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.
Time Frame Up to Day 112

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Albumin, Visit1 , Day 1, Pre-dose, Low
1
5.9%
0
0%
0
0%
1
12.5%
Albumin, Visit 2 , Day 5, Low
0
0%
0
0%
0
0%
1
12.5%
Albumin, Visit 3 , Day 10, Pre-dose, Low
0
0%
0
0%
0
0%
1
12.5%
Albumin, Visit 3 , Day 10, 3 hour, Low
0
0%
0
0%
0
0%
1
12.5%
Albumin, Visit 5 , Day 60, Low
0
0%
0
0%
0
0%
1
12.5%
ALT, visit 4, day 30, high
0
0%
0
0%
1
11.1%
0
0%
ALT, Visit 6, Day 90, High
0
0%
0
0%
0
0%
1
12.5%
ALT, Visit 7, Day 112, High
0
0%
0
0%
0
0%
1
12.5%
AST, Visit 4, Day 30, High
1
5.9%
0
0%
1
11.1%
0
0%
AST, Visit 6, Day 90, High
0
0%
0
0%
0
0%
1
12.5%
AST, Visit 7, Day 112, High
0
0%
0
0%
0
0%
1
12.5%
Calcium, Visit1 , Day 1, Pre-dose, Low
2
11.8%
0
0%
1
11.1%
1
12.5%
Calcium, Visit1 , Day 1, 24 hour, Low
1
5.9%
1
12.5%
1
11.1%
0
0%
CO2, Visit 1, Day 1, Pre-dose, Low
5
29.4%
3
37.5%
6
66.7%
5
62.5%
CO2, Visit 1, Day 1, 24 hour, Low
3
17.6%
3
37.5%
1
11.1%
3
37.5%
CO2, Visit 2, Day 5, Low
3
17.6%
1
12.5%
3
33.3%
4
50%
CO2, Visit 3, Day 10, Pre-dose, Low
2
11.8%
0
0%
1
11.1%
2
25%
CO2, Visit 3, Day 10, 3H, Low
3
17.6%
0
0%
1
11.1%
1
12.5%
CO2, Visit 4, Day 30, Low
2
11.8%
1
12.5%
2
22.2%
1
12.5%
CO2, Visit 5, Day 60, Low
1
5.9%
0
0%
1
11.1%
0
0%
CO2, Visit 6, Day 90, Low
2
11.8%
1
12.5%
0
0%
0
0%
CO2, Visit 7, Day 112, Low
4
23.5%
1
12.5%
0
0%
1
12.5%
CO2, Early Withdrawal, Low
1
5.9%
Creatinine, Visit1 , Day 1, Pre-dose, High
0
0%
0
0%
1
11.1%
0
0%
Creatinine, Visit 2 , Day 5, High
0
0%
0
0%
1
11.1%
0
0%
Creatinine, Visit 3, Day 10, Pre-dose, High
0
0%
0
0%
1
11.1%
1
12.5%
Creatinine, Visit 3, Day 10, 3 hour, High
0
0%
0
0%
1
11.1%
1
12.5%
Creatinine, Visit 4, Day 30, High
0
0%
0
0%
1
11.1%
0
0%
Creatinine, Visit 5, Day 60, High
0
0%
0
0%
1
11.1%
0
0%
Creatinine, Visit 6 Day 90, High
0
0%
0
0%
1
11.1%
0
0%
Glucose, Visit 1, Day 1, Pre-dose, High
0
0%
0
0%
2
22.2%
1
12.5%
Glucose, Visit 1, Day 1, Pre-dose, Low
0
0%
0
0%
1
11.1%
0
0%
Glucose, Visit 1, Day 1, 24 hour, High
3
17.6%
0
0%
1
11.1%
3
37.5%
Glucose, Visit 1, Day 1, 24 hour, Low
1
5.9%
0
0%
0
0%
0
0%
Glucose, Visit 2, Day 5, High
2
11.8%
0
0%
2
22.2%
1
12.5%
Glucose, Visit 3, Day 10, Pre-dose, High
2
11.8%
0
0%
2
22.2%
0
0%
Glucose, Visit 3, Day 10, 3 hour, High
1
5.9%
0
0%
1
11.1%
1
12.5%
Glucose, Visit 4, Day 30, High
0
0%
0
0%
1
11.1%
1
12.5%
Glucose, Visit 5, Day 60, High
0
0%
1
12.5%
2
22.2%
0
0%
Glucose, Visit 6, Day 90, High
0
0%
1
12.5%
0
0%
0
0%
Glucose, Visit 7, Day 112, High
0
0%
1
12.5%
1
11.1%
0
0%
Potassium, Visit 1, Day 1, 24 hour, High
2
11.8%
0
0%
0
0%
0
0%
Potassium, Visit 3, Day 10, Pre-dose, High
1
5.9%
0
0%
0
0%
1
12.5%
Potassium, Visit 5, Day 60, High
0
0%
0
0%
1
11.1%
0
0%
Sodium, Visit 2, Day 5, Low
1
5.9%
0
0%
0
0%
0
0%
Sodium, Visit 3, Day 10, 3 hour, Low
1
5.9%
0
0%
0
0%
0
0%
Sodium, Visit 4, Day 30, Low
1
5.9%
0
0%
0
0%
0
0%
7. Primary Outcome
Title Number of Participants With Abnormal Hematological Parameters
Description 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.
Time Frame Up to Day 112

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Lymphocytes, Visit 1, Day 1, Pre-dose, Low
0
0%
0
0%
1
11.1%
0
0%
Lymphocytes, Visit 1, Day 1, 24 hour, Low
0
0%
0
0%
1
11.1%
0
0%
Lymphocytes, Visit 2, Day 5, Low
1
5.9%
0
0%
0
0%
0
0%
Lymphocytes, Visit 6, Day 90, Low
1
5.9%
0
0%
0
0%
0
0%
Lymphocytes, Visit 7, Day 112, Low
1
5.9%
0
0%
0
0%
0
0%
Lymphocytes, Early withdrawal, Low
1
5.9%
Total Neutrophils, Visit 5, Day 60, Low
1
5.9%
0
0%
0
0%
0
0%
Total Neutrophils, Visit 6, Day 90, Low
1
5.9%
0
0%
0
0%
0
0%
Platelet count, Visit 4, Day 30, High
1
5.9%
0
0%
0
0%
0
0%
Platelet count, Visit 5, Day 60, High
1
5.9%
0
0%
0
0%
0
0%
8. Secondary Outcome
Title Number of Participants With Positive Antibodies to GSK249320
Description 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.
Time Frame Day 1, 5, 10, 30, 60, 90 and 112

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 1 Day 1 True positive
0
0%
0
0%
1
11.1%
0
0%
Visit 3 Day 10 True positive
0
0%
1
12.5%
1
11.1%
0
0%
Visit 4 Day 30 True positive
0
0%
0
0%
1
11.1%
0
0%
Visit 5 Day 60 True positive
0
0%
0
0%
1
11.1%
0
0%
9. Secondary Outcome
Title 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)
Description 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.
Time Frame Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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
Measure Participants 8 9 8
AUC(0-inf)
15.20
(4.049)
71.01
(14.426)
192.88
(75.413)
AUC(0-t), Dose 1
4.12
(0.643)
17.25
(3.704)
51.07
(18.719)
AUC(0-t), Dose 2
25.64
(7.272)
118.38
(28.885)
365.63
(83.891)
10. Secondary Outcome
Title Mean Maximum Observed Concentration (Cmax) and Last Observed Quantifiable Concentration (Ct)
Description 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.
Time Frame Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population. Only those participants with data available for analysis were analyzed.
Arm/Group Title GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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
Measure Participants 8 9 8
Cmax, Dose 1
38.62
(8.832)
157.42
(25.814)
508.20
(74.468)
Cmax, Dose 2
53.06
(17.650)
215.71
(30.617)
756.98
(178.150)
Ct, Dose 1
14.9528
(3.63064)
59.3422
(22.10706)
192.1709
(92.75262)
Ct, Dose 2
0.6647
(0.35900)
6.8148
(4.04066)
22.1555
(17.84140)
11. Secondary Outcome
Title Mean Time of Occurrence of Cmax (Tmax) and Time of Last Observed Quantifiable Concentration (Tlast)
Description 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.
Time Frame Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Outcome Measure Data

Analysis Population Description
Pharmacokinetics population. Only those participants with data available for analysis were analyzed.
Arm/Group Title GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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
Measure Participants 8 9 8
tmax, Dose 1
2.723
(3.8135)
1.807
(1.7017)
1.885
(1.8745)
tmax, Dose 2
2.013
(1.0562)
1.618
(1.1276)
1.874
(1.0792)
tlast, Dose 1
207.43
(26.247)
192.67
(39.911)
205.47
(83.950)
tlast, Dose 2
2901.11
(144.034)
2539.06
(418.783)
2403.84
(141.350)
12. Secondary Outcome
Title Mean Terminal Phase Half-life (t1/2)
Description 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.
Time Frame Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Outcome Measure Data

Analysis Population Description
Pharmacokinetics population. Only those participants with data available for analysis were analyzed.
Arm/Group Title GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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
Measure Participants 8 9 8
Mean (Standard Deviation) [Day]
21.11
(3.121)
24.01
(5.240)
24.01
(8.551)
13. Secondary Outcome
Title Mean Terminal Phase Rate Constant ( Lambda-Z)
Description 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.
Time Frame Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Outcome Measure Data

Analysis Population Description
Pharmacokinetics population. Only those participants with data available for analysis were analyzed.
Arm/Group Title GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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
Measure Participants 8 9 8
lambda-z, Dose 1
0.00138
(0.000191)
0.00126
(0.000292)
0.00130
(0.000327)
lambda-z, Dose 2
0.00139
(0.000207)
0.00126
(0.000281)
0.00130
(0.000327)
14. Secondary Outcome
Title Mean Clearance of GSK249320
Description 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).
Time Frame Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Outcome Measure Data

Analysis Population Description
Pharmacokinetics population. Only those participants with data available for analysis were analyzed.
Arm/Group Title GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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
Measure Participants 8 9 7
Mean (Standard Deviation) [mL/hour/killogram (kg)]
0.0700
(0.01835)
0.0750
(0.01545)
0.0886
(0.03652)
15. Secondary Outcome
Title Mean Change in Mean Gait Velocity
Description 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.
Time Frame Baseline (Day 5), Day 30, 60, 90, 112

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 4 Day 30
-0.010
(0.4021)
0.548
(0.6015)
0.649
(0.6114)
0.210
(0.3957)
Visit 5 Day 60
0.252
(0.4005)
0.679
(0.7587)
0.730
(0.8277)
0.203
(0.7378)
Visit 6 Day 90
0.207
(0.3327)
0.925
(0.7199)
0.539
(0.7267)
0.302
(0.4770)
Visit 7 Day 112
0.376
(0.4164)
1.052
(0.6678)
1.047
(0.8208)
0.408
(0.5011)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
-0.03 to 0.92
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.231
Estimation Comments Mean difference = GSK249320 1 mg/kg - Placebo
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.25 to 1.13
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.214
Estimation Comments Mean difference = GSK249320 5 mg/kg - Placebo
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
-0.20 to 0.80
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.246
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
-0.24 to 0.95
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.292
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
-0.05 to 1.09
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.279
Estimation Comments Mean difference= GSK249320 5 mg/kg- Placebo
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.61 to 0.69
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.319
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.15 to 1.11
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.235
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
-0.06 to 0.86
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.225
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
-0.29 to 0.77
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.259
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.10 to 1.12
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.251
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.09 to 1.08
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.242
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.39 to 0.73
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.277
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo
16. Secondary Outcome
Title Mean Change in Berg Balance Scale (BBS) Total Score
Description 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.
Time Frame Baseline (Day 5), Day 30, 60, 90 and 112

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 4 Day 30
6.8
(14.35)
17.5
(12.94)
14.8
(17.05)
5.7
(10.25)
Visit 5 Day 60
10.7
(16.29)
21.7
(18.83)
19.0
(17.78)
12.2
(18.58)
Visit 6 Day 90
13.5
(16.47)
24.4
(18.88)
20.4
(19.94)
-0.2
(6.72)
Visit 7 Day 112
14.6
(18.75)
25.4
(20.56)
24.7
(18.96)
11.8
(18.12)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.56
Confidence Interval (2-Sided) 95%
-0.60 to 19.71
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.981
Estimation Comments Mean difference =GSK249320 1 mg/kg - Placebo
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.47
Confidence Interval (2-Sided) 95%
-1.32 to 18.26
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.801
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-11.1 to 11.24
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.470
Estimation Comments Mean difference= GSK249320 GSK249320 15 mg/kg - Placebo
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 11.58
Confidence Interval (2-Sided) 95%
0.01 to 23.15
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.631
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.77
Confidence Interval (2-Sided) 95%
-2.35 to 19.89
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.411
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
-12.2 to 13.21
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.195
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.66
Confidence Interval (2-Sided) 95%
-1.34 to 20.66
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.351
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.45
Confidence Interval (2-Sided) 95%
-3.22 to 18.13
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.198
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -10.63
Confidence Interval (2-Sided) 95%
-22.9 to 1.60
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.959
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.59
Confidence Interval (2-Sided) 95%
-3.07 to 22.24
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.134
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.89
Confidence Interval (2-Sided) 95%
-6.37 to 18.15
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.948
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.11
Confidence Interval (2-Sided) 95%
-17.1 to 10.84
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.768
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo
17. Secondary Outcome
Title Mean Change in Total Fugl-Meyer Motor (FM) Assessment
Description 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.
Time Frame Baseline (Day 5), Day 30 and 112

Outcome Measure Data

Analysis Population Description
All subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Total Score, Visit 4 Day 30
10.2
(19.19)
8.8
(10.51)
17.0
(18.23)
3.1
(21.56)
Total Score, Visit 7 Day 112
19.6
(23.13)
17.3
(20.96)
25.3
(28.40)
8.7
(34.59)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.47
Confidence Interval (2-Sided) 95%
-15.81 to 12.86
Parameter Dispersion Type: Standard Error of the Mean
Value: 7.047
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 9.86
Confidence Interval (2-Sided) 95%
-4.08 to 23.80
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.852
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -5.40
Confidence Interval (2-Sided) 95%
-20.41 to 9.60
Parameter Dispersion Type: Standard Error of the Mean
Value: 7.376
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -2.40
Confidence Interval (2-Sided) 95%
-22.87 to 18.07
Parameter Dispersion Type: Standard Error of the Mean
Value: 10.040
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 5.03
Confidence Interval (2-Sided) 95%
-15.95 to 26.00
Parameter Dispersion Type: Standard Error of the Mean
Value: 10.310
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo. Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -10.07
Confidence Interval (2-Sided) 95%
-32.29 to 12.15
Parameter Dispersion Type: Standard Error of the Mean
Value: 10.916
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change in Total Fugl-Meyer assessment= Treatment + Visit + Treatment * Visit + Baseline
18. Secondary Outcome
Title Mean Change in Total Box and Blocks Transferred on Affected Side
Description 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.
Time Frame Baseline (Day 1), Day 30, 60, 90 and 112

Outcome Measure Data

Analysis Population Description
All subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 4 Day 30
8.5
(11.02)
8.6
(9.01)
11.3
(11.30)
13.0
(13.83)
Visit 5 Day 60
13.83
(12.33)
14.6
(18.45)
15.6
(13.41)
10.9
(13.57)
Visit 6 Day 90
15.5
(14.11)
16.1
(15.68)
18.0
(15.18)
14.8
(16.50)
Visit 7 Day 112
16.5
(14.18)
18.8
(15.22)
18.3
(19.67)
15.2
(15.55)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-10.4 to 10.61
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.147
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.75
Confidence Interval (2-Sided) 95%
-7.75 to 13.26
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.157
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.85
Confidence Interval (2-Sided) 95%
-6.17 to 15.88
Parameter Dispersion Type: Standard Error of the Mean
Value: 5.409
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
-12.1 to 14.45
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.504
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.05
Confidence Interval (2-Sided) 95%
-11.0 to 15.12
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.426
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.22
Confidence Interval (2-Sided) 95%
-16.1 to 11.68
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.820
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
-12.9 to 14.18
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.664
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.03
Confidence Interval () 95%
-12.4 to 14.43
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.595
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.95
Confidence Interval (2-Sided) 95%
-15.2 to 13.32
Parameter Dispersion Type: Standard Error of the Mean
Value: 7.020
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
-11.9 to 16.40
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.953
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.52
Confidence Interval (2-Sided) 95%
-10.5 to 17.55
Parameter Dispersion Type: Standard Error of the Mean
Value: 6.909
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-15.4 to 14.39
Parameter Dispersion Type: Standard Error of the Mean
Value: 7.328
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
19. Secondary Outcome
Title Mean Change in Grip Strength on Affected Side
Description 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.
Time Frame Baseline (Day 1), Day 30, 60, 90 and 112

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 4 Day 30
-1.01
(9.291)
2.94
(5.897)
1.13
(6.200)
5.52
(6.526)
Visit 5 Day 60
2.64
(11.314)
5.50
(6.208)
1.25
(6.791)
4.57
(7.615)
Visit 6 Day 90
2.24
(10.811)
6.50
(8.118)
3.71
(8.236)
4.44
(7.644)
Visit 7 Day 112
2.74
(11.824)
6.58
(7.115)
1.28
(9.923)
6.78
(8.334)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.66
Confidence Interval (2-Sided) 95%
-5.33 to 8.65
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.420
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-7.56 to 6.96
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.550
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.56
Confidence Interval (2-Sided) 95%
-2.67 to 11.78
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.534
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.05
Confidence Interval (2-Sided) 95%
-5.78 to 9.89
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.841
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -2.35
Confidence Interval (2-Sided) 95%
-10.4 to 5.72
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.958
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 5
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.44
Confidence Interval (2-Sided) 95%
-6.68 to 9.55
Parameter Dispersion Type: Standard Error of the Mean
Value: 3.978
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.46
Confidence Interval (2-Sided) 95%
-4.94 to 11.85
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.109
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
-8.15 to 9.12
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.235
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
-7.97 to 9.50
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.280
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.04
Confidence Interval (2-Sided) 95%
-5.53 to 11.61
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.205
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.58
Confidence Interval (2-Sided) 95%
-11.5 to 6.32
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.376
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 7
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.73
Confidence Interval (2-Sided) 95%
-5.22 to 12.69
Parameter Dispersion Type: Standard Error of the Mean
Value: 4.396
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo. Affected Change from Baseline = Treatment + Visit + Treatment * Visit + Affected Baseline + Unaffected Baseline
20. Secondary Outcome
Title Number of Participants With Modified Rankin Scale (mRS)
Description 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.
Time Frame Day 30 and 90

Outcome Measure Data

Analysis Population Description
All subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
mRS Score 0
0
0%
0
0%
0
0%
0
0%
mRS Score 1
2
11.8%
2
25%
1
11.1%
2
25%
mRS Score 2
3
17.6%
1
12.5%
3
33.3%
0
0%
mRS Score 3
3
17.6%
3
37.5%
3
33.3%
3
37.5%
mRS Score 4
4
23.5%
2
25%
2
22.2%
2
25%
mRS Score 5
2
11.8%
0
0%
0
0%
0
0%
mRS Score 0
0
0%
1
12.5%
1
11.1%
0
0%
mRS Score 1
3
17.6%
1
12.5%
2
22.2%
2
25%
mRS Score 2
5
29.4%
2
25%
2
22.2%
1
12.5%
mRS Score 3
3
17.6%
4
50%
2
22.2%
0
0%
mRS Score 4
3
17.6%
0
0%
1
11.1%
2
25%
mRS Score 5
0
0%
0
0%
0
0%
1
12.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg, GSK249320 5 mg/kg, GSK249320 15 mg/kg
Comments Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.9260
Comments
Method Fisher Exact
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg, GSK249320 5 mg/kg, GSK249320 15 mg/kg
Comments Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.5647
Comments
Method Fisher Exact
Comments
21. Secondary Outcome
Title Change From Baseline of National Institutes of Health Stroke Scale (NIHSS)
Description 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.
Time Frame Baseline (Day 1), Day 10, 30 and 90

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 3 Day 10
-1.6
(1.79)
-3.1
(2.36)
-1.8
(1.72)
-4.4
(2.07)
Visit 4 Day 30
-3.7
(2.02)
-4.6
(2.13)
-4.0
(3.00)
-4.6
(2.23)
Visit 6 Day 90
-5.0
(2.91)
-6.3
(1.67)
-5.4
(2.77)
-2.7
(4.80)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 3
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.34
Confidence Interval (2-Sided) 95%
-3.17 to 0.49
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.896
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 3
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-1.95 to 1.57
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.861
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 3
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.92
Confidence Interval (2-Sided) 95%
-4.83 to -1.02
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.933
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.70
Confidence Interval (2-Sided) 95%
-2.47 to 1.08
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.868
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.27
Confidence Interval (2-Sided) 95%
-1.98 to 1.44
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.834
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.92
Confidence Interval (2-Sided) 95%
-2.77 to 0.92
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.904
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-3.64 to 1.57
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.278
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-2.97 to 2.24
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.278
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.66 to 1.408
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.21
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline = Treatment + Visit + Treatment * Visit + Baseline
22. Secondary Outcome
Title Mean Barthel Total Score
Description 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.
Time Frame Day 30 and 90

Outcome Measure Data

Analysis Population Description
All subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 4 Day 30
66.8
(36.19)
86.3
(23.41)
87.8
(20.63)
78.6
(22.86)
Visit 6 Day 90
81.8
(25.30)
97.5
(3.78)
92.5
(11.65)
74.2
(29.40)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 19.46
Confidence Interval (2-Sided) 95%
-6.11 to 45.04
Parameter Dispersion Type: Standard Error of the Mean
Value: 12.584
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 20.99
Confidence Interval (2-Sided) 95%
-3.66 to 45.64
Parameter Dispersion Type: Standard Error of the Mean
Value: 12.131
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 4
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 11.79
Confidence Interval (2-Sided) 95%
-14.9 to 38.50
Parameter Dispersion Type: Standard Error of the Mean
Value: 13.143
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 15.71
Confidence Interval (2-Sided) 95%
-2.63 to 34.06
Parameter Dispersion Type: Standard Error of the Mean
Value: 9.021
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 11.56
Confidence Interval (2-Sided) 95%
-6.38 to 29.50
Parameter Dispersion Type: Standard Error of the Mean
Value: 8.835
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -7.49
Confidence Interval (2-Sided) 95%
-27.1 to 12.08
Parameter Dispersion Type: Standard Error of the Mean
Value: 9.641
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Barthel Total Score= Treatment + Visit + Treatment *Visit
23. Secondary Outcome
Title Mean Total Montreal Cognitive Assessment (MoCA) Score
Description 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.
Time Frame Day 5 and 90

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 2 Day 5
19.4
(7.46)
18.0
(9.94)
15.2
(11.63)
21.6
(9.30)
Visit 6 Day 90
22.7
(5.27)
21.6
(7.60)
20.9
(8.72)
22.8
(9.93)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-4.12 to 3.43
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.849
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Day 90 MoCA = Treatment + Day 5 MoCA
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-3.96 to 3.62
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.856
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Day 90 MoCA = Treatment + Day 5 MoCA
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.15
Confidence Interval (2-Sided) 95%
-5.31 to 3.01
Parameter Dispersion Type: Standard Error of the Mean
Value: 2.037
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Day 90 MoCA = Treatment + Day 5 MoCA
24. Secondary Outcome
Title Mean Geriatric Depression Scale (GDS)
Description 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.
Time Frame Day 5 and 90

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 2 Day 5
4.5
(4.15)
2.1
(1.36)
5.1
(3.68)
3.6
(2.67)
Visit 6 Day 90
4.5
(3.48)
2.8
(1.83)
6.1
(3.91)
3.8
(4.12)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Placebo Vs GSK249320 1 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-3.12 to 2.63
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.408
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo. Day 90 GDS Score= Treatment + Day 5 GDS Score
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Placebo Vs GSK249320 5 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
-1.20 to 4.30
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.347
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Day 90 GDS Score= Treatment + Day 5 GDS Score
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Placebo Vs GSK249320 15 mg/kg, Visit 6
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-3.09 to 2.98
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.486
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo. Day 90 GDS Score= Treatment+Day 5 GDS Score
25. Secondary Outcome
Title Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level
Description 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.
Time Frame Baseline (Day 1), Day 30 and 112

Outcome Measure Data

Analysis Population Description
All subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Stimulation Level 100%, Visit 4 Day 30
0.289
(0.6046)
-0.068
(0.4125)
-1.560
(3.9411)
0.030
(0.1600)
Stimulation Level 100%, Visit 7 Day 112
-0.021
(0.1365)
0.116
(0.5811)
0.148
(0.3270)
0.465
(0.6293)
Stimulation Level 110%, Visit 4 Day 30
0.525
(0.9065)
1.420
(2.5622)
-1.535
(4.3653)
0.283
(0.6950)
Stimulation Level 110%, Visit 7 Day 112
0.168
(0.4176)
0.690
(1.0786)
0.298
(0.5837)
1.850
(2.5032)
Stimulation Level 120%, Visit 4 Day 30
0.741
(1.3249)
2.023
(1.8115)
-0.557
(4.9402)
0.640
(1.3393)
Stimulation Level 120%, Visit 7 Day 112
0.590
(1.5803)
0.728
(0.4908)
0.490
(0.4887)
3.035
(4.0093)
Stimulation Level 130%, Visit 4 Day 30
0.802
(1.6584)
1.180
(0.6988)
-0.697
(4.9586)
0.697
(1.6763)
Stimulation Level 130%, Visit 7 Day 112
0.636
(1.8215)
0.100
(1.0296)
0.706
(0.6750)
3.335
(4.4760)
Stimulation Level 140%, Visit 4 Day 30
1.042
(1.8231)
1.100
(1.5979)
-0.768
(4.6784)
0.867
(2.7265)
Stimulation Level 140%, Visit 7 Day 112
0.742
(2.1058)
-0.050
(1.6503)
0.954
(1.1362)
3.040
(4.0447)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 100%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.289
Confidence Interval (2-Sided) 95%
-0.841 to 0.264
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.2639
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 100%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.310
Confidence Interval (2-Sided) 95%
-0.862 to 0.241
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.2637
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 100%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -0.303
Confidence Interval (2-Sided) 95%
-0.966 to 0.361
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.3172
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 100%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.204
Confidence Interval (2-Sided) 95%
-0.184 to 0.593
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.1841
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 100%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.105
Confidence Interval (2-Sided) 95%
-0.284 to 0.494
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.1846
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 100%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.416
Confidence Interval (2-Sided) 95%
-0.132 to 0.965
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.2602
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 110%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.156
Confidence Interval (2-Sided) 95%
-0.650 to 2.961
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.8652
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 110%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.518
Confidence Interval (2-Sided) 95%
-2.249 to 1.213
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.8324
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 110%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.269
Confidence Interval (2-Sided) 95%
-2.436 to 1.898
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.0383
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 110%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.806
Confidence Interval (2-Sided) 95%
-0.420 to 2.031
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.5862
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 110%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.007
Confidence Interval (2-Sided) 95%
-1.183 to 1.168
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.5640
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 110%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.506
Confidence Interval (2-Sided) 95%
-0.064 to 3.077
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.7570
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 120%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.644
Confidence Interval (2-Sided) 95%
-1.056 to 4.344
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.2976
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 120%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.231
Confidence Interval (2-Sided) 95%
-2.681 to 2.219
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.1762
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 120%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.184
Confidence Interval (2-Sided) 95%
-3.279 to 2.910
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.4796
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 120%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.622
Confidence Interval (2-Sided) 95%
-1.428 to 2.672
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.9746
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 120%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.602
Confidence Interval (2-Sided) 95%
-2.560 to 1.356
Parameter Dispersion Type: Standard Error of the Mean
Value: 0.9340
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 120%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.063
Confidence Interval (2-Sided) 95%
-0.610 to 4.736
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.2810
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 130%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.556
Confidence Interval (2-Sided) 95%
-1.494 to 4.607
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.4588
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 130%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.531
Confidence Interval (2-Sided) 95%
-3.102 to 2.041
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.2336
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 130%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.185
Confidence Interval (2-Sided) 95%
-3.471 to 3.101
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.5697
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 130%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.686
Confidence Interval (2-Sided) 95%
-1.996 to 3.367
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.2689
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 130%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.556
Confidence Interval (2-Sided) 95%
-2.838 to 1.726
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.0822
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 130%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.219
Confidence Interval (2-Sided) 95%
-0.884 to 5.322
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.4792
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 140%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.631
Confidence Interval (2-Sided) 95%
-1.696 to 4.958
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.5890
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 140%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.508
Confidence Interval (2-Sided) 95%
-3.219 to 2.203
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.2985
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 140%, Visit 4 Day 30
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.110
Confidence Interval (2-Sided) 95%
-3.369 to 3.588
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.6603
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 1 mg/kg
Comments Stimulation Level 140%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.852
Confidence Interval (2-Sided) 95%
-2.446 to 4.150
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.5675
Estimation Comments Mean difference= GSK249320 1 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 5 mg/kg
Comments Stimulation Level 140%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.357
Confidence Interval (2-Sided) 95%
-3.074 to 2.359
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.2918
Estimation Comments Mean difference= GSK249320 5 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Placebo, GSK249320 15 mg/kg
Comments Stimulation Level 140%, Visit 7 Day 112
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.686
Confidence Interval (2-Sided) 95%
-1.937 to 5.308
Parameter Dispersion Type: Standard Error of the Mean
Value: 1.7306
Estimation Comments Mean difference= GSK249320 15 mg/kg - Placebo Change from Baseline= Treatment + Visit + Treatment* Visit + Baseline
26. Secondary Outcome
Title Serum Levels of the S100β Protein
Description 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.
Time Frame Day 1 (Pre-dose, Post dose 1, 6, 24 hour), Day 5

Outcome Measure Data

Analysis Population Description
All Subjects population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
Measure Participants 17 8 9 8
Visit 1, Day 1- Pre-dose
-1.021
(1.3655)
-1.224
(1.0676)
-0.978
(1.3218)
-1.624
(1.1256)
Visit 1, Day 1- 1 hour post-dose
-1.024
(1.2038)
-0.785
(1.3917)
-1.130
(1.4363)
-1.615
(1.2312)
Visit 1, Day 1 - 6 hour post-dose
-0.851
(1.4014)
-1.251
(1.0449)
-0.895
(1.4683)
-1.135
(0.7006)
Visit 1, Day 1 - 24 hour post-dose
-1.053
(1.4309)
-1.329
(0.9649)
-0.744
(1.3523)
-1.644
(1.0244)
Visit 2, Day 5
-1.050
(1.0039)
-1.697
(0.7264)
-0.920
(1.1960)
-1.821
(0.9974)

Adverse Events

Time Frame AEs were collected up to Day 112
Adverse Event Reporting Description All subject population was used to report AEs.
Arm/Group Title Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Arm/Group Description 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. 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. 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. 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
All Cause Mortality
Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/17 (0%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Serious Adverse Events
Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/17 (17.6%) 1/8 (12.5%) 3/9 (33.3%) 3/8 (37.5%)
Cardiac disorders
Myocardial infarction 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Tachycardia 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
General disorders
Pyrexia 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Infections and infestations
Helicobacter infection 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Peridiverticulitis 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Injury, poisoning and procedural complications
Post procedural complication 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Metabolism and nutrition disorders
Failure to thrive 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Nervous system disorders
Ischaemic stroke 1/17 (5.9%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Cerebral infarction 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Cerebrovascular accident 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Epilepsy 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Transient ischaemic attack 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Psychiatric disorders
Depression 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Renal and urinary disorders
Renal failure acute 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Vascular disorders
Peripheral arterial occlusive disease 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Other (Not Including Serious) Adverse Events
Placebo GSK249320 1 mg/kg GSK249320 5 mg/kg GSK249320 15 mg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 9/17 (52.9%) 6/8 (75%) 7/9 (77.8%) 5/8 (62.5%)
Blood and lymphatic system disorders
Anaemia 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Cardiac disorders
Atrial fibrillation 1/17 (5.9%) 0/8 (0%) 2/9 (22.2%) 0/8 (0%)
Angina pectoris 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Atrial flutter 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Atrioventricular block 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Atrioventricular block complete 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Bradycardia 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Sinus arrhythmia 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Tachycardia 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Eye disorders
Conjunctivitis 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Gastrointestinal disorders
Constipation 2/17 (11.8%) 2/8 (25%) 1/9 (11.1%) 0/8 (0%)
Diarrhoea 0/17 (0%) 2/8 (25%) 1/9 (11.1%) 0/8 (0%)
Dyspepsia 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Flatulence 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Nausea 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Vomiting 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
General disorders
Pyrexia 0/17 (0%) 1/8 (12.5%) 1/9 (11.1%) 1/8 (12.5%)
Hepatobiliary disorders
Cholelithiasis 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Infections and infestations
Bacterial infection 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Clostridial infection 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Fungal skin infection 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Gastrointestinal infection 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Nasopharyngitis 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Urinary tract infection 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Investigations
Blood albumin decreased 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Protein total abnormal 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Metabolism and nutrition disorders
Hypokalaemia 1/17 (5.9%) 1/8 (12.5%) 1/9 (11.1%) 0/8 (0%)
Dehydration 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Glucose tolerance impaired 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Hypercholesterolaemia 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Hypoglycaemia 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Vitamin B12 deficiency 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Musculoskeletal and connective tissue disorders
Arthralgia 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Muscle spasms 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Nervous system disorders
Headache 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Cerebrovascular accident 0/17 (0%) 0/8 (0%) 0/9 (0%) 1/8 (12.5%)
Dysgeusia 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Psychiatric disorders
Insomnia 1/17 (5.9%) 2/8 (25%) 1/9 (11.1%) 1/8 (12.5%)
Restlessness 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Respiratory, thoracic and mediastinal disorders
Apnoeic attack 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Dyspnoea 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)
Nasal obstruction 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Throat tightness 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Skin and subcutaneous tissue disorders
Blister 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Pruritus generalised 1/17 (5.9%) 0/8 (0%) 0/9 (0%) 0/8 (0%)
Rash 0/17 (0%) 1/8 (12.5%) 0/9 (0%) 0/8 (0%)
Vascular disorders
Hypertension 0/17 (0%) 0/8 (0%) 1/9 (11.1%) 0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00833989
Other Study ID Numbers:
  • 111539
First Posted:
Feb 2, 2009
Last Update Posted:
Nov 17, 2017
Last Verified:
Sep 1, 2017