Trial Outcomes & Findings for Safety Escalating Repeat IV, in Stroke Patients (NCT NCT00833989)

Last Updated: 2017-11-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Up to 112 days

Results posted on

2017-11-17

Participant Flow

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.

A total of 42 participants were randomized and included in All subject population.

Participant milestones

Participant milestones
Measure	Placebo Eligible participants received 0.9% Sodium chloride as an intravenous (IV) infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks.	GSK249320 1 mg/kg Eligible participants received GSK249320, 1 milligram per kilogram (mg/kg)of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks.	GSK249320 5 mg/kg Eligible participants received GSK249320, 5mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks.	GSK249320 15 mg/kg Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks
Overall Study STARTED	17	8	9	8
Overall Study COMPLETED	14	8	8	6
Overall Study NOT COMPLETED	3	0	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Eligible participants received 0.9% Sodium chloride as an intravenous (IV) infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks.	GSK249320 1 mg/kg Eligible participants received GSK249320, 1 milligram per kilogram (mg/kg)of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks.	GSK249320 5 mg/kg Eligible participants received GSK249320, 5mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks.	GSK249320 15 mg/kg Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks
Overall Study Physician Decision	0	0	0	1
Overall Study Withdrawal by Subject	3	0	1	1

Baseline Characteristics

Safety Escalating Repeat IV, in Stroke Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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 n=42 Participants Total of all reporting groups
Age, Continuous	67.6 Year STANDARD_DEVIATION 10.79 • n=5 Participants	62.1 Year STANDARD_DEVIATION 13.01 • n=7 Participants	63.9 Year STANDARD_DEVIATION 13.76 • n=5 Participants	59.3 Year STANDARD_DEVIATION 12.99 • n=4 Participants	64.2 Year STANDARD_DEVIATION 12.27 • n=21 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	23 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	19 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	7 Participants n=4 Participants	40 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	00 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 112 days

Population: All Subjects population was defined as all participants who receive at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any AE	11 Participants	6 Participants	8 Participants	6 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any SAE	3 Participants	1 Participants	3 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to 112 days

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 30 minute, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 1 hour, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 1 hour, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 2 hour, High	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 4 hour, High	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 8 hour, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 12 hour, High	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 12 hour, Low	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 1, Day 1, 24 hour, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 6, Day 90, Low	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance SBP, Visit 7, Day 112, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance DBP, Visit 1, Day 1, 15 minute, Low	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance DBP, Visit 1, Day 1, 1 hour, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance DBP, Visit 1, Day 1, 2 hour, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance DBP, Visit 1, Day 1, 2 hour, Low	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance DBP, Visit 1, Day 1, 4 hour, High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance DBP, Visit 1, Day 1, 12 hour, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance DBP, Visit 2, Day 5, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance DBP, Visit 3, Day 10, 30 minute, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 1, Day 1, 0 hour, High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 1, Day 1, 15 minute, High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 1, Day 1, 30 minute, High	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 1, Day 1, 45 minute, High	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 1, Day 1, 1 hour, High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 1, Day 1, 2 hour, High	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 1, Day 1, 12 hour, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 1, Day 1, 24 hour, High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 2, Day 5, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 3, Day 10, 0 hour, High	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 3, Day 10, 15 minute, High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 3, Day 10, 30 minute, High	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 3, Day 10, 45 minute, High	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 3, Day 10, 1 hour, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 3, Day 10, 3 hour, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Changes of Potential Clinical Importance HR, Visit 4, Day 30, High	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 112 days

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 1, Day 1, Predose	2 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 1, Day 1, 24 hour	2 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 2, Day 5	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 3, Day 10, Predose	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 3, Day 10, 3 hour	2 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 4, Day 30	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 5, Day 60	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 6, Day 90	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Values Outside Range of Potential Clinical Importance Visit 7, Day 112	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 5 and 30 and at early withdrawal

Population: All Subject population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With Nerve Conduction Testing (NCT) Values Sensory, Early Withdrawal, Normal,	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Motor, Visit 2, Day 5, Normal	11 Participants	7 Participants	7 Participants	4 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Motor, Visit 2, Day 5, Abnormal, secondary to	4 Participants	1 Participants	2 Participants	4 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Motor, Visit 4, Day 30, Normal	11 Participants	7 Participants	6 Participants	4 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Motor, Visit 4, Day 30, Abnormal, secondary to	3 Participants	1 Participants	2 Participants	3 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Motor, Early Withdrawal, Abnormal, secondary to	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Sensory, Visit 2, Day 5, Normal	9 Participants	4 Participants	6 Participants	3 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Sensory, Visit 2, Day 5, Abnormal, secondary to	5 Participants	4 Participants	3 Participants	5 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Sensory, Not done	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Sensory, Visit 4, Day 30, Normal	12 Participants	5 Participants	7 Participants	3 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Sensory, Visit 4, Day 30, Abnormal, secondary to	2 Participants	3 Participants	1 Participants	4 Participants
Number of Participants With Nerve Conduction Testing (NCT) Values Sensory, Early Withdrawal, Abnormal, secondary to	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 60

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) White matter change, Day 10 compared to Day 1	9 Participants	5 Participants	5 Participants	2 Participants
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) White matter change, Day 60 compared to Day 1	6 Participants	6 Participants	2 Participants	3 Participants
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) White matter change, Day 60 compared to Day 10	5 Participants	5 Participants	1 Participants	3 Participants
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) Demyelination, Day 10 compared to Day 1, Yes	1 Participants	0 Participants	3 Participants	0 Participants
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) Demyelination, Day 10 compared to Day 1, No	13 Participants	8 Participants	6 Participants	7 Participants
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) Demyelination, Day 60 compared to Day 1, No	14 Participants	8 Participants	9 Participants	6 Participants
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) Demyelination, Day 60 compared to Day 10, No	14 Participants	8 Participants	9 Participants	6 Participants
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) Demyelination, During Study, Yes	2 Participants	0 Participants	3 Participants	0 Participants
Number of Participants With White Matter Changes and Demyelination Assessed by Magnetic Resonance Imaging (MRI) Demyelination, During Study, No	13 Participants	8 Participants	6 Participants	7 Participants

PRIMARY outcome

Timeframe: Up to Day 112

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With Abnormal Clinical Chemistry Parameters Albumin, Visit1 , Day 1, Pre-dose, Low	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Albumin, Visit 2 , Day 5, Low	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Albumin, Visit 3 , Day 10, Pre-dose, Low	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Albumin, Visit 3 , Day 10, 3 hour, Low	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Albumin, Visit 5 , Day 60, Low	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters ALT, visit 4, day 30, high	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters ALT, Visit 6, Day 90, High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters ALT, Visit 7, Day 112, High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters AST, Visit 4, Day 30, High	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters AST, Visit 6, Day 90, High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters AST, Visit 7, Day 112, High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Calcium, Visit1 , Day 1, Pre-dose, Low	2 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Calcium, Visit1 , Day 1, 24 hour, Low	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 1, Day 1, Pre-dose, Low	5 Participants	3 Participants	6 Participants	5 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 1, Day 1, 24 hour, Low	3 Participants	3 Participants	1 Participants	3 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 2, Day 5, Low	3 Participants	1 Participants	3 Participants	4 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 3, Day 10, Pre-dose, Low	2 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 3, Day 10, 3H, Low	3 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 4, Day 30, Low	2 Participants	1 Participants	2 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 5, Day 60, Low	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 6, Day 90, Low	2 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Visit 7, Day 112, Low	4 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters CO2, Early Withdrawal, Low	1 Participants	—	—	—
Number of Participants With Abnormal Clinical Chemistry Parameters Creatinine, Visit1 , Day 1, Pre-dose, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Creatinine, Visit 2 , Day 5, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Creatinine, Visit 3, Day 10, Pre-dose, High	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Creatinine, Visit 3, Day 10, 3 hour, High	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Creatinine, Visit 4, Day 30, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Creatinine, Visit 5, Day 60, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Creatinine, Visit 6 Day 90, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 1, Day 1, Pre-dose, High	0 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 1, Day 1, Pre-dose, Low	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 1, Day 1, 24 hour, High	3 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 1, Day 1, 24 hour, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 2, Day 5, High	2 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 3, Day 10, Pre-dose, High	2 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 3, Day 10, 3 hour, High	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 4, Day 30, High	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 5, Day 60, High	0 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 6, Day 90, High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Glucose, Visit 7, Day 112, High	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Potassium, Visit 1, Day 1, 24 hour, High	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Potassium, Visit 3, Day 10, Pre-dose, High	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Potassium, Visit 5, Day 60, High	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Sodium, Visit 2, Day 5, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Sodium, Visit 3, Day 10, 3 hour, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Parameters Sodium, Visit 4, Day 30, Low	1 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With Abnormal Hematological Parameters Lymphocytes, Visit 1, Day 1, Pre-dose, Low	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Hematological Parameters Lymphocytes, Visit 1, Day 1, 24 hour, Low	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Hematological Parameters Lymphocytes, Visit 2, Day 5, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Hematological Parameters Lymphocytes, Visit 6, Day 90, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Hematological Parameters Lymphocytes, Visit 7, Day 112, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Hematological Parameters Lymphocytes, Early withdrawal, Low	1 Participants	—	—	—
Number of Participants With Abnormal Hematological Parameters Total Neutrophils, Visit 5, Day 60, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Hematological Parameters Total Neutrophils, Visit 6, Day 90, Low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Hematological Parameters Platelet count, Visit 4, Day 30, High	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Hematological Parameters Platelet count, Visit 5, Day 60, High	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1, 5, 10, 30, 60, 90 and 112

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With Positive Antibodies to GSK249320 Visit 1 Day 1 True positive	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Positive Antibodies to GSK249320 Visit 3 Day 10 True positive	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Positive Antibodies to GSK249320 Visit 4 Day 30 True positive	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Positive Antibodies to GSK249320 Visit 5 Day 60 True positive	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants 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.	GSK249320 1 mg/kg n=9 Participants 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.	GSK249320 5 mg/kg n=8 Participants 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.	GSK249320 15 mg/kg Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks
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) AUC(0-inf)	15.20 Hour*mg/millilitre (mL) Standard Deviation 4.049	71.01 Hour*mg/millilitre (mL) Standard Deviation 14.426	192.88 Hour*mg/millilitre (mL) Standard Deviation 75.413	—
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) AUC(0-t), Dose 1	4.12 Hour*mg/millilitre (mL) Standard Deviation 0.643	17.25 Hour*mg/millilitre (mL) Standard Deviation 3.704	51.07 Hour*mg/millilitre (mL) Standard Deviation 18.719	—
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) AUC(0-t), Dose 2	25.64 Hour*mg/millilitre (mL) Standard Deviation 7.272	118.38 Hour*mg/millilitre (mL) Standard Deviation 28.885	365.63 Hour*mg/millilitre (mL) Standard Deviation 83.891	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Population: Pharmacokinetic population. Only those participants with data available for analysis were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants 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.	GSK249320 1 mg/kg n=9 Participants 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.	GSK249320 5 mg/kg n=8 Participants 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.	GSK249320 15 mg/kg Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks
Mean Maximum Observed Concentration (Cmax) and Last Observed Quantifiable Concentration (Ct) Cmax, Dose 1	38.62 microgram (ug) per mL Standard Deviation 8.832	157.42 microgram (ug) per mL Standard Deviation 25.814	508.20 microgram (ug) per mL Standard Deviation 74.468	—
Mean Maximum Observed Concentration (Cmax) and Last Observed Quantifiable Concentration (Ct) Cmax, Dose 2	53.06 microgram (ug) per mL Standard Deviation 17.650	215.71 microgram (ug) per mL Standard Deviation 30.617	756.98 microgram (ug) per mL Standard Deviation 178.150	—
Mean Maximum Observed Concentration (Cmax) and Last Observed Quantifiable Concentration (Ct) Ct, Dose 1	14.9528 microgram (ug) per mL Standard Deviation 3.63064	59.3422 microgram (ug) per mL Standard Deviation 22.10706	192.1709 microgram (ug) per mL Standard Deviation 92.75262	—
Mean Maximum Observed Concentration (Cmax) and Last Observed Quantifiable Concentration (Ct) Ct, Dose 2	0.6647 microgram (ug) per mL Standard Deviation 0.35900	6.8148 microgram (ug) per mL Standard Deviation 4.04066	22.1555 microgram (ug) per mL Standard Deviation 17.84140	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Population: Pharmacokinetics population. Only those participants with data available for analysis were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants 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.	GSK249320 1 mg/kg n=9 Participants 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.	GSK249320 5 mg/kg n=8 Participants 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.	GSK249320 15 mg/kg Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks
Mean Time of Occurrence of Cmax (Tmax) and Time of Last Observed Quantifiable Concentration (Tlast) tmax, Dose 1	2.723 hour Standard Deviation 3.8135	1.807 hour Standard Deviation 1.7017	1.885 hour Standard Deviation 1.8745	—
Mean Time of Occurrence of Cmax (Tmax) and Time of Last Observed Quantifiable Concentration (Tlast) tmax, Dose 2	2.013 hour Standard Deviation 1.0562	1.618 hour Standard Deviation 1.1276	1.874 hour Standard Deviation 1.0792	—
Mean Time of Occurrence of Cmax (Tmax) and Time of Last Observed Quantifiable Concentration (Tlast) tlast, Dose 1	207.43 hour Standard Deviation 26.247	192.67 hour Standard Deviation 39.911	205.47 hour Standard Deviation 83.950	—
Mean Time of Occurrence of Cmax (Tmax) and Time of Last Observed Quantifiable Concentration (Tlast) tlast, Dose 2	2901.11 hour Standard Deviation 144.034	2539.06 hour Standard Deviation 418.783	2403.84 hour Standard Deviation 141.350	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Population: Pharmacokinetics population. Only those participants with data available for analysis were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants 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.	GSK249320 1 mg/kg n=9 Participants 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.	GSK249320 5 mg/kg n=8 Participants 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.	GSK249320 15 mg/kg Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks
Mean Terminal Phase Half-life (t1/2)	21.11 Day Standard Deviation 3.121	24.01 Day Standard Deviation 5.240	24.01 Day Standard Deviation 8.551	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Population: Pharmacokinetics population. Only those participants with data available for analysis were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants 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.	GSK249320 1 mg/kg n=9 Participants 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.	GSK249320 5 mg/kg n=8 Participants 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.	GSK249320 15 mg/kg Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks
Mean Terminal Phase Rate Constant ( Lambda-Z) lambda-z, Dose 1	0.00138 1/ hour Standard Deviation 0.000191	0.00126 1/ hour Standard Deviation 0.000292	0.00130 1/ hour Standard Deviation 0.000327	—
Mean Terminal Phase Rate Constant ( Lambda-Z) lambda-z, Dose 2	0.00139 1/ hour Standard Deviation 0.000207	0.00126 1/ hour Standard Deviation 0.000281	0.00130 1/ hour Standard Deviation 0.000327	—

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, 1, 3, 6, 12 and 24 hour) and Day 10 (Pre-dose, 1, 3 hour)

Population: Pharmacokinetics population. Only those participants with data available for analysis were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=8 Participants 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.	GSK249320 1 mg/kg n=9 Participants 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.	GSK249320 5 mg/kg n=7 Participants 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.	GSK249320 15 mg/kg Eligible participants received GSK249320, 15mg/kg of body weight as an IV infusion via a programmable infusion pump. Each participant received two IV doses 9 ±1 days apart, where the first dose was administered 24-72 hours post stroke. Assessments for safety, pharmacokinetics and pharmacodynamics markers were extended to at least 16 weeks
Mean Clearance of GSK249320	0.0700 mL/hour/killogram (kg) Standard Deviation 0.01835	0.0750 mL/hour/killogram (kg) Standard Deviation 0.01545	0.0886 mL/hour/killogram (kg) Standard Deviation 0.03652	—

SECONDARY outcome

Timeframe: Baseline (Day 5), Day 30, 60, 90, 112

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Change in Mean Gait Velocity Visit 7 Day 112	0.376 Meters/second Standard Deviation 0.4164	1.052 Meters/second Standard Deviation 0.6678	1.047 Meters/second Standard Deviation 0.8208	0.408 Meters/second Standard Deviation 0.5011
Mean Change in Mean Gait Velocity Visit 4 Day 30	-0.010 Meters/second Standard Deviation 0.4021	0.548 Meters/second Standard Deviation 0.6015	0.649 Meters/second Standard Deviation 0.6114	0.210 Meters/second Standard Deviation 0.3957
Mean Change in Mean Gait Velocity Visit 5 Day 60	0.252 Meters/second Standard Deviation 0.4005	0.679 Meters/second Standard Deviation 0.7587	0.730 Meters/second Standard Deviation 0.8277	0.203 Meters/second Standard Deviation 0.7378
Mean Change in Mean Gait Velocity Visit 6 Day 90	0.207 Meters/second Standard Deviation 0.3327	0.925 Meters/second Standard Deviation 0.7199	0.539 Meters/second Standard Deviation 0.7267	0.302 Meters/second Standard Deviation 0.4770

SECONDARY outcome

Timeframe: Baseline (Day 5), Day 30, 60, 90 and 112

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Change in Berg Balance Scale (BBS) Total Score Visit 4 Day 30	6.8 Score on Scale Standard Deviation 14.35	17.5 Score on Scale Standard Deviation 12.94	14.8 Score on Scale Standard Deviation 17.05	5.7 Score on Scale Standard Deviation 10.25
Mean Change in Berg Balance Scale (BBS) Total Score Visit 5 Day 60	10.7 Score on Scale Standard Deviation 16.29	21.7 Score on Scale Standard Deviation 18.83	19.0 Score on Scale Standard Deviation 17.78	12.2 Score on Scale Standard Deviation 18.58
Mean Change in Berg Balance Scale (BBS) Total Score Visit 6 Day 90	13.5 Score on Scale Standard Deviation 16.47	24.4 Score on Scale Standard Deviation 18.88	20.4 Score on Scale Standard Deviation 19.94	-0.2 Score on Scale Standard Deviation 6.72
Mean Change in Berg Balance Scale (BBS) Total Score Visit 7 Day 112	14.6 Score on Scale Standard Deviation 18.75	25.4 Score on Scale Standard Deviation 20.56	24.7 Score on Scale Standard Deviation 18.96	11.8 Score on Scale Standard Deviation 18.12

SECONDARY outcome

Timeframe: Baseline (Day 5), Day 30 and 112

Population: All subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Change in Total Fugl-Meyer Motor (FM) Assessment Total Score, Visit 4 Day 30	10.2 Score on Scale Standard Deviation 19.19	8.8 Score on Scale Standard Deviation 10.51	17.0 Score on Scale Standard Deviation 18.23	3.1 Score on Scale Standard Deviation 21.56
Mean Change in Total Fugl-Meyer Motor (FM) Assessment Total Score, Visit 7 Day 112	19.6 Score on Scale Standard Deviation 23.13	17.3 Score on Scale Standard Deviation 20.96	25.3 Score on Scale Standard Deviation 28.40	8.7 Score on Scale Standard Deviation 34.59

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 30, 60, 90 and 112

Population: All subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Change in Total Box and Blocks Transferred on Affected Side Visit 4 Day 30	8.5 Blocks Standard Deviation 11.02	8.6 Blocks Standard Deviation 9.01	11.3 Blocks Standard Deviation 11.30	13.0 Blocks Standard Deviation 13.83
Mean Change in Total Box and Blocks Transferred on Affected Side Visit 5 Day 60	13.83 Blocks Standard Deviation 12.33	14.6 Blocks Standard Deviation 18.45	15.6 Blocks Standard Deviation 13.41	10.9 Blocks Standard Deviation 13.57
Mean Change in Total Box and Blocks Transferred on Affected Side Visit 6 Day 90	15.5 Blocks Standard Deviation 14.11	16.1 Blocks Standard Deviation 15.68	18.0 Blocks Standard Deviation 15.18	14.8 Blocks Standard Deviation 16.50
Mean Change in Total Box and Blocks Transferred on Affected Side Visit 7 Day 112	16.5 Blocks Standard Deviation 14.18	18.8 Blocks Standard Deviation 15.22	18.3 Blocks Standard Deviation 19.67	15.2 Blocks Standard Deviation 15.55

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 30, 60, 90 and 112

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Change in Grip Strength on Affected Side Visit 5 Day 60	2.64 Kg Standard Deviation 11.314	5.50 Kg Standard Deviation 6.208	1.25 Kg Standard Deviation 6.791	4.57 Kg Standard Deviation 7.615
Mean Change in Grip Strength on Affected Side Visit 6 Day 90	2.24 Kg Standard Deviation 10.811	6.50 Kg Standard Deviation 8.118	3.71 Kg Standard Deviation 8.236	4.44 Kg Standard Deviation 7.644
Mean Change in Grip Strength on Affected Side Visit 7 Day 112	2.74 Kg Standard Deviation 11.824	6.58 Kg Standard Deviation 7.115	1.28 Kg Standard Deviation 9.923	6.78 Kg Standard Deviation 8.334
Mean Change in Grip Strength on Affected Side Visit 4 Day 30	-1.01 Kg Standard Deviation 9.291	2.94 Kg Standard Deviation 5.897	1.13 Kg Standard Deviation 6.200	5.52 Kg Standard Deviation 6.526

SECONDARY outcome

Timeframe: Day 30 and 90

Population: All subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Number of Participants With Modified Rankin Scale (mRS) Visit 4 Day 30 · mRS Score 0	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 4 Day 30 · mRS Score 1	2 Participants	2 Participants	1 Participants	2 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 4 Day 30 · mRS Score 2	3 Participants	1 Participants	3 Participants	0 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 4 Day 30 · mRS Score 3	3 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 4 Day 30 · mRS Score 4	4 Participants	2 Participants	2 Participants	2 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 4 Day 30 · mRS Score 5	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 6 Day 90 · mRS Score 0	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 6 Day 90 · mRS Score 1	3 Participants	1 Participants	2 Participants	2 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 6 Day 90 · mRS Score 2	5 Participants	2 Participants	2 Participants	1 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 6 Day 90 · mRS Score 3	3 Participants	4 Participants	2 Participants	0 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 6 Day 90 · mRS Score 4	3 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Modified Rankin Scale (mRS) Visit 6 Day 90 · mRS Score 5	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 10, 30 and 90

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) Visit 3 Day 10	-1.6 Score on scale Standard Deviation 1.79	-3.1 Score on scale Standard Deviation 2.36	-1.8 Score on scale Standard Deviation 1.72	-4.4 Score on scale Standard Deviation 2.07
Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) Visit 4 Day 30	-3.7 Score on scale Standard Deviation 2.02	-4.6 Score on scale Standard Deviation 2.13	-4.0 Score on scale Standard Deviation 3.00	-4.6 Score on scale Standard Deviation 2.23
Change From Baseline of National Institutes of Health Stroke Scale (NIHSS) Visit 6 Day 90	-5.0 Score on scale Standard Deviation 2.91	-6.3 Score on scale Standard Deviation 1.67	-5.4 Score on scale Standard Deviation 2.77	-2.7 Score on scale Standard Deviation 4.80

SECONDARY outcome

Timeframe: Day 30 and 90

Population: All subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Barthel Total Score Visit 6 Day 90	81.8 Score on scale Standard Deviation 25.30	97.5 Score on scale Standard Deviation 3.78	92.5 Score on scale Standard Deviation 11.65	74.2 Score on scale Standard Deviation 29.40
Mean Barthel Total Score Visit 4 Day 30	66.8 Score on scale Standard Deviation 36.19	86.3 Score on scale Standard Deviation 23.41	87.8 Score on scale Standard Deviation 20.63	78.6 Score on scale Standard Deviation 22.86

SECONDARY outcome

Timeframe: Day 5 and 90

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Total Montreal Cognitive Assessment (MoCA) Score Visit 2 Day 5	19.4 Score on scale Standard Deviation 7.46	18.0 Score on scale Standard Deviation 9.94	15.2 Score on scale Standard Deviation 11.63	21.6 Score on scale Standard Deviation 9.30
Mean Total Montreal Cognitive Assessment (MoCA) Score Visit 6 Day 90	22.7 Score on scale Standard Deviation 5.27	21.6 Score on scale Standard Deviation 7.60	20.9 Score on scale Standard Deviation 8.72	22.8 Score on scale Standard Deviation 9.93

SECONDARY outcome

Timeframe: Day 5 and 90

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Geriatric Depression Scale (GDS) Visit 2 Day 5	4.5 Score on scale Standard Deviation 4.15	2.1 Score on scale Standard Deviation 1.36	5.1 Score on scale Standard Deviation 3.68	3.6 Score on scale Standard Deviation 2.67
Mean Geriatric Depression Scale (GDS) Visit 6 Day 90	4.5 Score on scale Standard Deviation 3.48	2.8 Score on scale Standard Deviation 1.83	6.1 Score on scale Standard Deviation 3.91	3.8 Score on scale Standard Deviation 4.12

SECONDARY outcome

Timeframe: Baseline (Day 1), Day 30 and 112

Population: All subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 100%, Visit 4 Day 30	0.289 Percent change in stimulation Standard Deviation 0.6046	-0.068 Percent change in stimulation Standard Deviation 0.4125	-1.560 Percent change in stimulation Standard Deviation 3.9411	0.030 Percent change in stimulation Standard Deviation 0.1600
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 100%, Visit 7 Day 112	-0.021 Percent change in stimulation Standard Deviation 0.1365	0.116 Percent change in stimulation Standard Deviation 0.5811	0.148 Percent change in stimulation Standard Deviation 0.3270	0.465 Percent change in stimulation Standard Deviation 0.6293
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 110%, Visit 4 Day 30	0.525 Percent change in stimulation Standard Deviation 0.9065	1.420 Percent change in stimulation Standard Deviation 2.5622	-1.535 Percent change in stimulation Standard Deviation 4.3653	0.283 Percent change in stimulation Standard Deviation 0.6950
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 110%, Visit 7 Day 112	0.168 Percent change in stimulation Standard Deviation 0.4176	0.690 Percent change in stimulation Standard Deviation 1.0786	0.298 Percent change in stimulation Standard Deviation 0.5837	1.850 Percent change in stimulation Standard Deviation 2.5032
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 120%, Visit 4 Day 30	0.741 Percent change in stimulation Standard Deviation 1.3249	2.023 Percent change in stimulation Standard Deviation 1.8115	-0.557 Percent change in stimulation Standard Deviation 4.9402	0.640 Percent change in stimulation Standard Deviation 1.3393
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 120%, Visit 7 Day 112	0.590 Percent change in stimulation Standard Deviation 1.5803	0.728 Percent change in stimulation Standard Deviation 0.4908	0.490 Percent change in stimulation Standard Deviation 0.4887	3.035 Percent change in stimulation Standard Deviation 4.0093
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 130%, Visit 4 Day 30	0.802 Percent change in stimulation Standard Deviation 1.6584	1.180 Percent change in stimulation Standard Deviation 0.6988	-0.697 Percent change in stimulation Standard Deviation 4.9586	0.697 Percent change in stimulation Standard Deviation 1.6763
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 130%, Visit 7 Day 112	0.636 Percent change in stimulation Standard Deviation 1.8215	0.100 Percent change in stimulation Standard Deviation 1.0296	0.706 Percent change in stimulation Standard Deviation 0.6750	3.335 Percent change in stimulation Standard Deviation 4.4760
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 140%, Visit 4 Day 30	1.042 Percent change in stimulation Standard Deviation 1.8231	1.100 Percent change in stimulation Standard Deviation 1.5979	-0.768 Percent change in stimulation Standard Deviation 4.6784	0.867 Percent change in stimulation Standard Deviation 2.7265
Mean Change in Transcranial Magnetic Stimulations (TMS) Evaluated by Peak to Peak MEP by % Stimulation Level Stimulation Level 140%, Visit 7 Day 112	0.742 Percent change in stimulation Standard Deviation 2.1058	-0.050 Percent change in stimulation Standard Deviation 1.6503	0.954 Percent change in stimulation Standard Deviation 1.1362	3.040 Percent change in stimulation Standard Deviation 4.0447

SECONDARY outcome

Timeframe: Day 1 (Pre-dose, Post dose 1, 6, 24 hour), Day 5

Population: All Subjects population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants 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.	GSK249320 1 mg/kg n=8 Participants 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.	GSK249320 5 mg/kg n=9 Participants 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.	GSK249320 15 mg/kg n=8 Participants 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
Serum Levels of the S100β Protein Visit 1, Day 1- Pre-dose	-1.021 log (ug per liter) Standard Deviation 1.3655	-1.224 log (ug per liter) Standard Deviation 1.0676	-0.978 log (ug per liter) Standard Deviation 1.3218	-1.624 log (ug per liter) Standard Deviation 1.1256
Serum Levels of the S100β Protein Visit 1, Day 1- 1 hour post-dose	-1.024 log (ug per liter) Standard Deviation 1.2038	-0.785 log (ug per liter) Standard Deviation 1.3917	-1.130 log (ug per liter) Standard Deviation 1.4363	-1.615 log (ug per liter) Standard Deviation 1.2312
Serum Levels of the S100β Protein Visit 1, Day 1 - 6 hour post-dose	-0.851 log (ug per liter) Standard Deviation 1.4014	-1.251 log (ug per liter) Standard Deviation 1.0449	-0.895 log (ug per liter) Standard Deviation 1.4683	-1.135 log (ug per liter) Standard Deviation 0.7006
Serum Levels of the S100β Protein Visit 1, Day 1 - 24 hour post-dose	-1.053 log (ug per liter) Standard Deviation 1.4309	-1.329 log (ug per liter) Standard Deviation 0.9649	-0.744 log (ug per liter) Standard Deviation 1.3523	-1.644 log (ug per liter) Standard Deviation 1.0244
Serum Levels of the S100β Protein Visit 2, Day 5	-1.050 log (ug per liter) Standard Deviation 1.0039	-1.697 log (ug per liter) Standard Deviation 0.7264	-0.920 log (ug per liter) Standard Deviation 1.1960	-1.821 log (ug per liter) Standard Deviation 0.9974

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

GSK249320 1 mg/kg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

GSK249320 5 mg/kg

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

GSK249320 15 mg/kg

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=17 participants at risk 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.	GSK249320 1 mg/kg n=8 participants at risk 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.	GSK249320 5 mg/kg n=9 participants at risk 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.	GSK249320 15 mg/kg n=8 participants at risk 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
Nervous system disorders Ischaemic stroke	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Nervous system disorders Cerebral infarction	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Nervous system disorders Cerebrovascular accident	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Nervous system disorders Epilepsy	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Nervous system disorders Transient ischaemic attack	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Myocardial infarction	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Tachycardia	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
General disorders Pyrexia	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Infections and infestations Helicobacter infection	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Infections and infestations Peridiverticulitis	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Injury, poisoning and procedural complications Post procedural complication	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Psychiatric disorders Depression	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Renal and urinary disorders Renal failure acute	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.

Measure	Placebo n=17 participants at risk 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.	GSK249320 1 mg/kg n=8 participants at risk 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.	GSK249320 5 mg/kg n=9 participants at risk 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.	GSK249320 15 mg/kg n=8 participants at risk 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
Gastrointestinal disorders Constipation	11.8% 2/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	25.0% 2/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Gastrointestinal disorders Diarrhoea	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	25.0% 2/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Gastrointestinal disorders Dyspepsia	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Gastrointestinal disorders Flatulence	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Gastrointestinal disorders Nausea	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Gastrointestinal disorders Vomiting	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Metabolism and nutrition disorders Hypokalaemia	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Metabolism and nutrition disorders Dehydration	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Metabolism and nutrition disorders Glucose tolerance impaired	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Metabolism and nutrition disorders Vitamin B12 deficiency	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Infections and infestations Bacterial infection	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Infections and infestations Clostridial infection	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Infections and infestations Fungal skin infection	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Infections and infestations Gastrointestinal infection	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Infections and infestations Nasopharyngitis	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Infections and infestations Urinary tract infection	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Psychiatric disorders Insomnia	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	25.0% 2/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Psychiatric disorders Restlessness	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Atrial fibrillation	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	22.2% 2/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Angina pectoris	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Atrial flutter	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Atrioventricular block	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Atrioventricular block complete	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Bradycardia	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Sinus arrhythmia	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Cardiac disorders Tachycardia	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Nervous system disorders Headache	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Nervous system disorders Cerebrovascular accident	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Nervous system disorders Dysgeusia	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
General disorders Pyrexia	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Musculoskeletal and connective tissue disorders Arthralgia	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Respiratory, thoracic and mediastinal disorders Apnoeic attack	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Respiratory, thoracic and mediastinal disorders Nasal obstruction	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Respiratory, thoracic and mediastinal disorders Throat tightness	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Skin and subcutaneous tissue disorders Blister	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Skin and subcutaneous tissue disorders Pruritus generalised	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Skin and subcutaneous tissue disorders Rash	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Investigations Blood albumin decreased	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Investigations Protein total abnormal	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	12.5% 1/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Blood and lymphatic system disorders Anaemia	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Eye disorders Conjunctivitis	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Hepatobiliary disorders Cholelithiasis	5.9% 1/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.
Vascular disorders Hypertension	0.00% 0/17 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.	11.1% 1/9 • AEs were collected up to Day 112 All subject population was used to report AEs.	0.00% 0/8 • AEs were collected up to Day 112 All subject population was used to report AEs.