Cerebrovascular Accident
Conditions
Keywords
Ischemic Stroke
Brief summary
Study MAG104615, a Proof of Concept Study for GSK249320 versus placebo in Stroke Patients.
Detailed description
Myelin-associated glycoprotein (MAG) is one of the key proteins known to inhibit neuronal regeneration when released from oligodendrocytes in conditions of neuronal injury, such as stroke. GSK249320 is a humanised monoclonal antibody (mAb) that binds with high specificity to MAG and antagonises or neutralises MAG-mediated inhibition and has been shown to improve functional recovery after stroke in pre-clinical models, possibly by promoting neuroregeneration and plasticity. The present study (MAG104615) is designed to establish Proof of Concept (PoC) for GSK249320 in ischemic stroke patients. MAG104615 will be a placebo-controlled, double-blind, multicenter, randomized, repeat dose, Bayesian design study. PoC will be achieved by demonstrating a clinically meaningful improvement in lower limb motor recovery, specifically by evaluating changes in gait velocity from baseline to Day 90/Month 3. Subjects will also be followed out to Day 180/Month 6 to further evaluate longer term motor recovery and safety. Additional secondary efficacy measures of motor recovery will be evaluated to further demonstrate and characterize the extent and duration of overall motor recovery after treatment with GSK249320. Changes in disability and neurological impairment will be characterized after treatment with GSK249320 and explored for how they relate to motor recovery. This PoC study will also further characterize the safety, PK, and immunogenicity of GSK249320 will explore pharmacodynamic (PD) markers, and will explore use of actigraphy to measure motor recovery. Subjects will be stratified by gait velocity at baseline for randomization (1:1 allocation) into one of two treatment groups: 15mg/kg GSK249320, or placebo. Each subject will receive 2 repeat IV doses of GSK249320 or placebo.
Interventions
DRUGGSK249320 100/mg
Clear to opalescent, colorless to pale yellow or pale brown, and is supplied as a sterile, concentrated solution (1000mg/vial). GSK249320 is for IV use only.
DRUGPlacebo
Placebo is a clear, colorless solution (50mM acetate buffer, pH 5.5 containing 0.02% (w/v) polysorbate-80 and made isotonic with 111.2 mM sodium chloride). Placebo is for intravenous (IV) use only.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Have a confirmed diagnosis of stroke according to the World Health Organization definition which is, 'a rapid onset event of vascular origin reflecting a focal disturbance of cerebral function, excluding isolated impairments of higher function, and persisting longer than 24 hours \[World Health Organization, 1989\]. * Stroke onset must be within the last 24-72 hours of the first infusion of Investigational Product. Time of stroke onset is defined at the time at which the patient/relative is first aware of the stroke deficit. For patients who awake with deficits, or who are found unconscious, the time of onset is defined as the time at which they were last known to be symptom free. * Have a stroke that is radiologically confirmed to be ischemic and supratentorial. The diameter of the ischemic lesion is \>15mm in any single direction or the volume is \>4cc. See the Study Procedures Manual (SPM) for guidance on how to calculate the lesion size. * Have a total NIHSS score of 3-21. * Have a lower limb deficit from the incident stroke which is defined as a score of 1-4 on the NIHSS Motor Leg question (question #6). * Aged 18-90, inclusive. * Expectation the subject will receive standard physical, occupational and speech rehabilitation therapy as indicated for the post stroke deficits. * Male subjects and female subjects of non-child-bearing and child-bearing potential are allowed to participate in this study. See Section 11, Appendix 1 for definitions. Females of child-bearing potential must have a negative pregnancy test prior to enrollment and must agree to use one of the contraceptive methods specified in Section 11, Appendix 1.
Exclusion criteria
* Ability to walk \>0.8m/s as measured by the Gait Velocity assessment. * History of a previous symptomatic stroke within 3 months prior to study entry. * Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke Rankin score of \>2. * Subjects who are not alert or are unresponsive as defined by a score of 2 or 3 on the NIHSS Level of Consciousness question (Question 1a). * Presence of significant aphasia likely to confound or interfere with completion of the study assessments. * Presence of a significant pre-existing gait deficit prior to study entry that is likely to confound clinical evaluations * Presence of pre-existing neurologic or psychiatric disease which is active and not adequately controlled such that it interfered with major activities of daily living immediately prior to the current stroke and is likely to interfere with study participation/visits or confound clinical evaluations. * The subject poses a significant suicide risk, in the opinion of the investigator. * Current or chronic history of liver disease, known hepatic or biliary abnormalities (except Gilbert's syndrome or asymptomatic gallstones), or known history of hepatitis B or hepatitis C infection. A positive hepatitis B or hepatitis C result on the GSK labs drawn at baseline/Study Day 1 do not exclude a subject from continuing in the study unless there are associated clinical signs/symptoms of liver disease; however, the subject should be treated as clinically indicated and the GSK Medical Monitor should be contacted for further discussion. * Presence of either a central or peripheral demyelinating disease, such as multiple sclerosis or IgM monoclonal gammopathy of unknown significance (MGUS). * Expected death due to the incident stroke, or evidence of a chronic co-morbid condition or unstable acute systemic illness which, in the opinion of the investigator, could shorten the subject's survival such that it would limit his/her ability to complete the study. * Presence of the following ECG values on baseline ECG: QTc \> 500 msec (using either Bazett's formula (QTcB) or Fridericia's formula (QTcF)); or uncorrected QT \>600msec (machine or manual over-read). If the ECG indicates a prolonged QTc interval value outside these limits, two further ECGs should be performed during the same sitting and the average QTc value of these triplicate ECGs calculated. If the average value exceeds the stated limits, the subject is not eligible. * Participation in any investigational rehabilitation paradigm targeting stroke recovery during the duration of this study. * Have a contraindication to MRI as per local hospital practice/guidelines. * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Prior treatment with GSK249320. * History of sensitivity to Investigational Product excipients (acetate buffer, polysorbate 80 and sodium chloride) that, in the opinion of the investigator or GSK Medical Monitor, contraindicates the subject's participation. * Pregnant females as determined by positive urine hCG test prior to enrollment. * Lactating females. * Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline (BL) to Month 3/ Day 90 in Gait Velocity | BL (Day 1) and Month 3/Day 90 | Gait is the way or manner in which a person walks. Gait velocity (walking speed) is an objective, quantitative measure of lower extremity motor recovery in individuals who have had a stroke. Participants were asked to walk at their usual pace over a level, indoor 10 meter (m) distance and were allowed to use their normal assistive devices. The time (seconds\[s\]) taken by the participants to travel the 10 m distance was recorded. Gait velocity (m/s) as assessed by study personnel was derived as: 10 divided by time to walk 10 m. Two trials of gait velocity were conducted at each time point. Change from BL was calculated as the mean Month 3/Day 90 value minus the mean BL value. BL was defined as Day 1. The measure type displayed are posterior means. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | BL (Day 1), Month 1/Day 30, Month 2/Day 60, Month 3/Day 90 and Month 6/Day 180. | Participants were categorized at each visit into the following gait velocity categories: 0 m/s, \>0 to \<0.4 m/s, \>=0.4 m/s to 0.8 m/s and \>0.8m/s. A distinction was made between participants who are too incapacitated to walk (i.e., gait velocity = 0m/s) and participants for whom the gait velocity assessment was not performed due to another reason (i.e., truly missing data). Participants were asked to walk at their usual or normal pace and using their normal assistive devices. Two trials of gait velocity were conducted at each time point. The number of participants transitioning from one gait velocity category to another category was assessed at each post-Baseline visit and was presented in terms of the following transition categories: worsened, no change, improved 1 level, improved 2 levels and improved 3 levels. By-visit sample sizes vary due to missing data or early termination of the study, missing data was not imputed. |
| Number of Falls Over Time | BL (Day 1), Day 90 and Day 180 | The number of participants who experienced 1, 2, 3 or \>=4 falls between BL to Day 90 and BL to Day 180 is summarized. By-visit sample sizes vary due to missing data or early termination of the study. The participants who experienced atleast one-fall were reported |
| Change From BL in Dexterity as Measured by Box and Blocks Test | BL (Day 1), Month 1/Day 30, Month 2/Day 60, Month 3/Day 90 and Month 6/Day 180 | Dexterity is ability of person to use hands skillfully in performing a task. Box and Blocks test is an objective, gross manual dexterity test in individuals with upper limb impairments. Participants were asked to move small wooden blocks from one side of a partitioned box to other. The score was determined by number of blocks transferred within a 60 second time period. Both affected and unaffected arms were tested, starting with the unaffected arm. Change from BL was calculated as the individual post- BL value minus BL value. A higher number of displaced blocks indicated a better gross dexterity and a low number of displaced blocks indicated poor gross dexterity. It was analyzed using fixed effects for treatment, visit, treatment by visit interaction, sex, age, Baseline National Institute of Health stroke scale (NIHSS) total score, BL number of blocks transferred by the affected and unaffected arms, country and presence of concomitant medications that potentially impact recovery. |
| Number of Participants Experiencing Falls | BL (Day 1) Day 90 and Day 180 | The number of participants who experienced at least one fall between BL to Day 90 and BL to Day 180 is summarized. |
| Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Up to 14 months | An AE is 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. A SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or all events of possible drug-induced liver injury with hyperbilirubinaemia. Medical or scientific judgment is exercised in other situations. |
| Number of Participants With Events Common to Stroke | From Day 1 until early withdrawal, death, Month 6/Day 180 | Events common to stroke were those events that commonly occurred after a stroke and are generally associated with the underlying stroke or the progression of stroke. These included joint or soft tissue pain, bladder incontinence, depression/mood disorder, urinary tract infection, dysphagia, bowel incontinence, dysarthia, confusion, spasticity, limb edema, aspiration pneumonia, hemorrhagic transformation (symptomatic or asymptomatic), pressure ulcers, progression of stroke, malnutrition, deep vein thrombosis, brain herniation, pulmonary embolism, seizures, and falls. |
| Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | BL (Day 1) , Day 6, Day 180 and early withdrawal (EW) visit | Safety was measured by monitoring vital signs including blood pressure. The BL for DBP and SBP was the value of pre-dose assessment on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From BL in Vitals Signs-Heart Rate | Day 1, Day 6, Day 180 and EW visit | Safety was measured by monitoring vital signs including heart rate. The BL for heart rate was the value of pre-dose assessment on Day 1. Change from BL was calculated as the individual post-BL value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. BL was defined as Day 1. |
| Change From BL in ECG Parameter-Heart Rate | BL (Day 1) Day 6, Day 30 and EW visit | A single 12-lead ECG was obtained at each time point that measured heart rate. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From BL in ECG Parameters | BL (Day 1), Day 6, Day 30 and EW visit | A single 12-lead ECG was obtained at each time point and the following ECG intervals were determined: PR, QRS, QT, RR and corrected QT (QTc), QT interval corrected by Bazett's formula (QTcB), QT interval corrected by Fridericia's formula (QTcF). BL for ECG parameters was the value of Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From BL in Clinical Chemistry- Albumin and Total Protein | BL (Day 1), Day 6, Day 30, Day 90 and Day 180 | ALB and TP were measured at BL, Day 6, Day 30, Day 90 and Day 180. Baseline was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | BL (Day 1), Day 6, Day 30, Day 90 and Day 180 | Ca, Cl, Gluc, K, Na and BUN were measured at BL, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | BL (Day 1), Day 6, Day 30, Day 90 and Day 180 | ALP, ALT and AST were measured at BL, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. |
| Mean Change From BL to Month 6/ Day 180 in Gait Velocity | BL (Day 1) and Month 6/Day 180 | Gait is the way or manner in which a person walks. Gait velocity (walking speed) is an objective, quantitative measure of lower extremity motor recovery in individuals who have had a stroke. Participants were asked to walk at their usual pace over a level, indoor 10 m distance and were allowed to use their normal assistive devices. The time (s) taken by the participants to travel the 10 m distance was recorded. Gait velocity (m/s) as assessed by study personnel was derived as: 10 divided by time to walk 10 m. Two trials of gait velocity were conducted at each time point. Change from BL was calculated as the mean Month 3/Day 90 value minus the mean BL value. BL was defined as Day 1. The measure type displayed are posterior means. |
| Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | BL (Day 1), Day 6, Day 30, Day 90 and Day 180 | EOS, LYM, Total ANC, PLT count and WBC count were measured at BL, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value.By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From BL in Hematology- Hemoglobin | BL (Day 1), Day 6, Day 30, Day 90 and Day 180 | Hemoglobin was measured at BL Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. . By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From Baseline in Hematology- Hematocrit | BL (Day 1), Day 6, Day 30, Day 90 and Day 180 | Hematocrit was measured at Baseline, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value.By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From BL in NIHSS Total Score | BL (Day 1), Day 30, Day 90 and Day 180 | The NIHSS is a 15 item, standardized, disease-specific, deficit scale which measures neurological impairment (level of consciousness, eye movements, visual fields, facial symmetry, motor strength (arm and leg), coordination, sensation, language (aphasia and dysarthria), and neglect) and is used to quantify participant status by measuring the severity of the stroke as assessed by NIHSS certified study personnel. The total NIHSS score is calculated as the sum of responses to the 15 items. The total NIHSS score ranges from 0-42, with a higher score indicative of a more severe impairment. By-visit sample sizes vary due to missing data or early termination of the study. Change from BL was calculated as the individual post-Baseline value minus the BL value. BL was defined as the value at Day 1. |
| Number of Participants With Suicidal Ideation Via Columbia Suicide Severity Rating Scale (CSSRS) | Da y 1, Da y 6, Day 30, Day 60, Day 90 and Day 180 | C-SSRS is a clinician-rated scale that evaluates severity and change of suicidality by integrating both suicidality behavior and ideation. For Suicidal Ideation (SI), participants were scored non-suicidal:0, wish to be dead:1, non-specific active suicidal thoughts:2, active suicidal ideation with associated thoughts of methods without intent:3, active suicidal ideation with some intent to act on suicidal thoughts without clear plan:4, active suicidal ideation with plan and intent:5 (most severe). SI intensity total score was the sum of suicidal ideation severity rating scores for frequency, duration, controllability, deterrents, and reasons for ideation. For each item, each participant got an intensity score from 0(none) to 5(worst). Therefore, the suicidal ideation intensity total score range from 0 to 25, with a score of 0 given for no suicidal ideation. |
| Maximum Observed Plasma Concentration (Cmax) for GSK249320 | Pre-dose and post-dose up to Day 180 | Cmax is the maximum observed concentration of GSK249320 obtained at the end of infusion post dose on Day 6. Due to early termination of the study, this data was not collected. |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) GSK249320 | Pre-dose and post-dose up to Day 180 | Tmax is the time of the occurrence of Cmax. The Cmax is defined as the maximum observed concentration of GSK249320 obtained at the end of infusion post dose on day 6. Due to early termination of the study data for Tmax was not collected. |
| PK as Measured by Plasma Decay Half-life (t1/2) GSK249320 | Up to Day 180 | Blood samples were collected for determination of plasma concentrations of GSK249320. Terminal phase half-life was derived from the plasma concentration-time data. Only participants in the GSK249320 15 mg/kg group were analyzed. |
| Area Under the Concentration-time Curve From 0 to 5 Days [AUC(0-5d)] and Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] for GSK249320 | Pre-dose and post-dose up to Day 180 | Blood samples were collected for determination of plasma concentrations of GSK249320. AUC (0-5d) and AUC (0-inf) were derived from the plasma concentration-time data. AUC(0-5d) is the model predicted AUC over the planned TAU of 5 days. Only participants in the GSK249320 15 mg/kg group were analyzed. |
| Clearance (CL) for GSK249320 | Up to Day 180 | Blood samples were collected for determination of plasma concentrations of GSK249320. CL was derived from the plasma concentration-time data. Analysis was performed for PK Population that comprised of all participants in the Safety Population who had at least one PK sample with a concentration above the non-quantifiable limit. Only participants in the GSK249320 15 mg/kg group were analyzed. |
| Volume of Distribution (V1 and V2) and Volume at Steady State (Vss) for GSK249320 | Up to Day 180 | Blood samples were collected for determination of plasma concentrations of GSK249320. V1, V2 and Vss were derived from the plasma concentration-time data. Analysis was performed for PK Population that comprised of all participants in the Safety Population who had at least one PK sample with a concentration above the non-quantifiable limit. Only participants in the GSK249320 15 mg/kg group were analyzed. |
| Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 1, Day 30, Day 180, EW visit and Follow-up visit | Blood samples were collected and the presence of antibodies against GSK249320 was assessed using ECL assays. Positive result indicated presence of antibodies and negative result indicated absence of antibodies. Confirmed samples with presence of antibodies were further characterized for neutralizing activity as binding antibody (BAb) and neutralising antibody (NAb) by a neutralization assay.By-visit sample sizes vary due to missing data or early termination of the study. |
| Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | BL (Day 1), Day 6, Day 30, Day 90 and Day 180 | Direct bilirubin, total bilirubin and creatinine were measured at BL, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. |
Countries
Canada, Germany, United Kingdom, United States
Participant flow
Recruitment details
A total of 134 participants with Stroke, were randomized to the study. The study was conducted from 18 May 2013 to 28 July 2014 at 30 centers; with 5 in United States, 5 in Canada, 8 in United Kingdom, and 12 in Germany. The ITT population consisted of total 120 participants and the Per Protocol consisted of 104 participants.
Pre-assignment details
Screening details: This study consisted of a 6 month Core study period and an Extended follow Up period, if required. The study was terminated early at the time of Interim Analysis for reasons of futility. At that time, a total of 134 participants were randomized, of which 133 participants had received at least one dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants were administered placebo as two IV infusions, the first on Study Day 1 which was 24-72 hours post-stroke onset, and the second on Study Day 6 (+/- 2 days). Each 100 mL, IV infusion was delivered over a period of 75 minutes (a 60 minute infusion followed by a 10 to 15 minute flush). | 68 |
| GSK249320 15 mg/kg Participants received GSK249320 15 mg/kg administered as two IV infusions, the first on Study Day 1 which is 24-72 post-stroke onset, and the second on Study Day 6 (+/- 2 days). Each 100 mL IV infusion was delivered over a period of 75 minutes (a 60 minute infusion followed by a 10 to 15 minute flush). | 65 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event, non-fatal | 2 | 0 |
| Overall Study | Consent withdrawn by subject | 6 | 7 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Study Closed/Terminated | 25 | 23 |
Baseline characteristics
| Characteristic | GSK249320 15 mg/kg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 11.92 | 67.6 years STANDARD_DEVIATION 11.53 | 67.1 years STANDARD_DEVIATION 11.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 62 Participants | 124 Participants | 62 Participants |
| Sex: Female, Male Female | 31 Participants | 60 Participants | 29 Participants |
| Sex: Female, Male Male | 34 Participants | 73 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 68 | 2 / 65 |
| other Total, other adverse events | 25 / 68 | 32 / 65 |
| serious Total, serious adverse events | 16 / 68 | 9 / 65 |
Outcome results
Primary
Mean Change From Baseline (BL) to Month 3/ Day 90 in Gait Velocity
Gait is the way or manner in which a person walks. Gait velocity (walking speed) is an objective, quantitative measure of lower extremity motor recovery in individuals who have had a stroke. Participants were asked to walk at their usual pace over a level, indoor 10 meter (m) distance and were allowed to use their normal assistive devices. The time (seconds\[s\]) taken by the participants to travel the 10 m distance was recorded. Gait velocity (m/s) as assessed by study personnel was derived as: 10 divided by time to walk 10 m. Two trials of gait velocity were conducted at each time point. Change from BL was calculated as the mean Month 3/Day 90 value minus the mean BL value. BL was defined as Day 1. The measure type displayed are posterior means.
Time frame: BL (Day 1) and Month 3/Day 90
Population: Intent-To-Treat (ITT) population comprised of participants who received at least 1 infusion of investigational product and had at least 1 post-Baseline efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline (BL) to Month 3/ Day 90 in Gait Velocity | 0.5417 m/s | Standard Deviation 0.062 |
| GSK249320 15 mg/kg | Mean Change From Baseline (BL) to Month 3/ Day 90 in Gait Velocity | 0.5859 m/s | Standard Deviation 0.0535 |
Comparison: Credible intervals are displayed as confidence intervals. Posterior means, standard deviations, and credible intervals are provided in the table.p-value: 0.71395% CI: [-0.119, 0.2]Bayesian method
Secondary
Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay
Blood samples were collected and the presence of antibodies against GSK249320 was assessed using ECL assays. Positive result indicated presence of antibodies and negative result indicated absence of antibodies. Confirmed samples with presence of antibodies were further characterized for neutralizing activity as binding antibody (BAb) and neutralising antibody (NAb) by a neutralization assay.By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: Day 1, Day 30, Day 180, EW visit and Follow-up visit
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 1, BAb Negative | 60 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 1, NAb Negative | 0 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 180, BAb Negative | 24 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 30, NAb Negative | 1 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | EW visit, BAb Positive | 1 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 30, BAb Positive | 4 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | EW visit, BAb Negative | 22 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 180, BAb Positive | 0 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | EW visit, NAb Negative | 1 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 30, BAb Negative | 44 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | FU visit, BAb Positive | 0 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | FU visit, NAb Negative | 0 Participants |
| Placebo | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 1, BAb Positive | 7 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | FU visit, NAb Negative | 1 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 1, BAb Positive | 5 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 1, BAb Negative | 59 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 1, NAb Negative | 2 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 30, BAb Positive | 4 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 30, BAb Negative | 46 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 30, NAb Negative | 1 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 180, BAb Positive | 5 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | Day 180, BAb Negative | 19 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | EW visit, BAb Positive | 4 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | EW visit, BAb Negative | 18 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | EW visit, NAb Negative | 4 Participants |
| GSK249320 15 mg/kg | Antibodies Against GSK249320, Assessed Using Electrochemi-luminescent Assay (ECL) Assay | FU visit, BAb Positive | 1 Participants |
Secondary
Area Under the Concentration-time Curve From 0 to 5 Days [AUC(0-5d)] and Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] for GSK249320
Blood samples were collected for determination of plasma concentrations of GSK249320. AUC (0-5d) and AUC (0-inf) were derived from the plasma concentration-time data. AUC(0-5d) is the model predicted AUC over the planned TAU of 5 days. Only participants in the GSK249320 15 mg/kg group were analyzed.
Time frame: Pre-dose and post-dose up to Day 180
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve From 0 to 5 Days [AUC(0-5d)] and Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] for GSK249320 | AUC(0-5 d) | 28.2273 Milligrams/milliliter*hour | Geometric Coefficient of Variation 10.9 |
| Placebo | Area Under the Concentration-time Curve From 0 to 5 Days [AUC(0-5d)] and Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time [AUC(0-inf)] for GSK249320 | AUC(0-inf) | 120.6895 Milligrams/milliliter*hour | Geometric Coefficient of Variation 20.4 |
Secondary
Change From Baseline in Hematology- Hematocrit
Hematocrit was measured at Baseline, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value.By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hematology- Hematocrit | Day 90 | -0.01446 Ratio | Standard Deviation 0.053418 |
| Placebo | Change From Baseline in Hematology- Hematocrit | Day 6 | 0.00096 Ratio | Standard Deviation 0.032094 |
| Placebo | Change From Baseline in Hematology- Hematocrit | Day 180 | -0.02455 Ratio | Standard Deviation 0.056181 |
| Placebo | Change From Baseline in Hematology- Hematocrit | Day 30 | -0.00350 Ratio | Standard Deviation 0.040669 |
| GSK249320 15 mg/kg | Change From Baseline in Hematology- Hematocrit | Day 180 | 0.01909 Ratio | Standard Deviation 0.043139 |
| GSK249320 15 mg/kg | Change From Baseline in Hematology- Hematocrit | Day 30 | 0.01116 Ratio | Standard Deviation 0.046146 |
| GSK249320 15 mg/kg | Change From Baseline in Hematology- Hematocrit | Day 6 | 0.00896 Ratio | Standard Deviation 0.032858 |
| GSK249320 15 mg/kg | Change From Baseline in Hematology- Hematocrit | Day 90 | 0.01329 Ratio | Standard Deviation 0.049054 |
Secondary
Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)
ALP, ALT and AST were measured at BL, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 30 | 11.7 International units per liter | Standard Deviation 21.47 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 6 | 7.7 International units per liter | Standard Deviation 20.05 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 90 | 8.6 International units per liter | Standard Deviation 27.18 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 180 | 8.9 International units per liter | Standard Deviation 12.73 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 6 | 11.4 International units per liter | Standard Deviation 25.92 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 30 | 7.9 International units per liter | Standard Deviation 19.02 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 90 | -0.8 International units per liter | Standard Deviation 16.14 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 180 | -2.0 International units per liter | Standard Deviation 12.83 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 6 | 7.9 International units per liter | Standard Deviation 26.39 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 30 | 0.2 International units per liter | Standard Deviation 14.24 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 90 | -6.1 International units per liter | Standard Deviation 11.78 |
| Placebo | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 180 | -3.2 International units per liter | Standard Deviation 7.13 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 90 | -5.2 International units per liter | Standard Deviation 13.33 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 90 | 3.2 International units per liter | Standard Deviation 11.21 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 6 | 6.2 International units per liter | Standard Deviation 16.4 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 30 | 19.5 International units per liter | Standard Deviation 35.87 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 30 | -0.9 International units per liter | Standard Deviation 13.18 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 90 | 6.7 International units per liter | Standard Deviation 18.01 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 180 | 1.4 International units per liter | Standard Deviation 10.66 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALP, Day 180 | 4.0 International units per liter | Standard Deviation 17.63 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 180 | -5.0 International units per liter | Standard Deviation 9.7 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 6 | 10.7 International units per liter | Standard Deviation 16.22 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | AST, Day 6 | 2.5 International units per liter | Standard Deviation 15.52 |
| GSK249320 15 mg/kg | Change From BL in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) | ALT, Day 30 | 10.6 International units per liter | Standard Deviation 27.84 |
Secondary
Change From BL in Clinical Chemistry- Albumin and Total Protein
ALB and TP were measured at BL, Day 6, Day 30, Day 90 and Day 180. Baseline was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Clinical Chemistry- Albumin and Total Protein | ALB, Day 6 | 0.0 Grams per liter | Standard Deviation 3.02 |
| Placebo | Change From BL in Clinical Chemistry- Albumin and Total Protein | ALB, Day 30 | 1.0 Grams per liter | Standard Deviation 3.44 |
| Placebo | Change From BL in Clinical Chemistry- Albumin and Total Protein | ALB, Day 90 | 2.3 Grams per liter | Standard Deviation 3.23 |
| Placebo | Change From BL in Clinical Chemistry- Albumin and Total Protein | ALB, Day 180 | 2.3 Grams per liter | Standard Deviation 3.8 |
| Placebo | Change From BL in Clinical Chemistry- Albumin and Total Protein | TP, Day 6 | 1.0 Grams per liter | Standard Deviation 4.64 |
| Placebo | Change From BL in Clinical Chemistry- Albumin and Total Protein | TP, Day 30 | 2.7 Grams per liter | Standard Deviation 5.13 |
| Placebo | Change From BL in Clinical Chemistry- Albumin and Total Protein | TP, Day 90 | 3.1 Grams per liter | Standard Deviation 4.92 |
| Placebo | Change From BL in Clinical Chemistry- Albumin and Total Protein | TP, Day 180 | 4.4 Grams per liter | Standard Deviation 5.07 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Albumin and Total Protein | TP, Day 180 | 7.6 Grams per liter | Standard Deviation 5.89 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Albumin and Total Protein | ALB, Day 6 | -0.2 Grams per liter | Standard Deviation 3.67 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Albumin and Total Protein | TP, Day 6 | 0.9 Grams per liter | Standard Deviation 5.9 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Albumin and Total Protein | ALB, Day 30 | 3.0 Grams per liter | Standard Deviation 5.5 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Albumin and Total Protein | TP, Day 90 | 6.5 Grams per liter | Standard Deviation 7.34 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Albumin and Total Protein | ALB, Day 90 | 4.4 Grams per liter | Standard Deviation 5.14 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Albumin and Total Protein | TP, Day 30 | 5.6 Grams per liter | Standard Deviation 8.11 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Albumin and Total Protein | ALB, Day 180 | 5.3 Grams per liter | Standard Deviation 3.86 |
Secondary
Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine
Direct bilirubin, total bilirubin and creatinine were measured at BL, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | direct bilirubin, Day 6 | 0.3 Micromoles per liter | Standard Deviation 3.81 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | direct bilirubin, Day 30 | -1.0 Micromoles per liter | Standard Deviation 1.93 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | direct bilirubin, Day 90 | -1.5 Micromoles per liter | Standard Deviation 1.92 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | direct bilirubin, Day 180 | -1.2 Micromoles per liter | Standard Deviation 1.59 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | total bilirubin, Day 6 | -1.5 Micromoles per liter | Standard Deviation 3.76 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | total bilirubin, Day 30 | -4.6 Micromoles per liter | Standard Deviation 4.9 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | total bilirubin, Day 90 | -4.9 Micromoles per liter | Standard Deviation 4.75 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | total bilirubin, Day 180 | -4.6 Micromoles per liter | Standard Deviation 4.83 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | creatinine, Day 6 | 2.35 Micromoles per liter | Standard Deviation 20.52 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | creatinine, Day 30 | 4.94 Micromoles per liter | Standard Deviation 31.767 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | creatinine, Day 90 | 6.69 Micromoles per liter | Standard Deviation 18.98 |
| Placebo | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | creatinine, Day 180 | 5.07 Micromoles per liter | Standard Deviation 12.925 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | creatinine, Day 90 | 3.09 Micromoles per liter | Standard Deviation 15.387 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | direct bilirubin, Day 6 | -0.0 Micromoles per liter | Standard Deviation 1.58 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | total bilirubin, Day 90 | -3.5 Micromoles per liter | Standard Deviation 5.59 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | direct bilirubin, Day 30 | -0.4 Micromoles per liter | Standard Deviation 1.48 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | creatinine, Day 30 | 9.79 Micromoles per liter | Standard Deviation 28.329 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | direct bilirubin, Day 90 | -0.5 Micromoles per liter | Standard Deviation 1.62 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | total bilirubin, Day 180 | -3.8 Micromoles per liter | Standard Deviation 5.28 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | direct bilirubin, Day 180 | -0.1 Micromoles per liter | Standard Deviation 1.38 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | creatinine, Day 180 | 0.24 Micromoles per liter | Standard Deviation 13.857 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | total bilirubin, Day 6 | -1.8 Micromoles per liter | Standard Deviation 5.9 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | creatinine, Day 6 | 3.48 Micromoles per liter | Standard Deviation 16.778 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry- Direct Bilirubin, Total Bilirubin, Creatinine | total bilirubin, Day 30 | -3.0 Micromoles per liter | Standard Deviation 4.85 |
Secondary
Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca)
Ca, Cl, Gluc, K, Na and BUN were measured at BL, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Na, Day 30 | -0.3 Millimoles per liter | Standard Deviation 2.64 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | K, Day 30 | 0.37 Millimoles per liter | Standard Deviation 0.487 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | K, Day 180 | 0.33 Millimoles per liter | Standard Deviation 0.517 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Urea/BUN, Day 90 | 1.02 Millimoles per liter | Standard Deviation 2.31 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Ca, Day 6 | 0.042 Millimoles per liter | Standard Deviation 0.1163 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Ca, Day 30 | 0.091 Millimoles per liter | Standard Deviation 0.1254 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Ca, Day 90 | 0.093 Millimoles per liter | Standard Deviation 0.1092 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Ca, Day 180 | 0.087 Millimoles per liter | Standard Deviation 0.1053 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Cl, Day 6 | -0.9 Millimoles per liter | Standard Deviation 3.13 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Cl, Day 90 | -1.3 Millimoles per liter | Standard Deviation 3.02 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Cl, Day 180 | -1.4 Millimoles per liter | Standard Deviation 2.48 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Gluc, Day 6 | 0.21 Millimoles per liter | Standard Deviation 3.123 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Gluc, Day 30 | -0.93 Millimoles per liter | Standard Deviation 2.611 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Gluc, Day 90 | -1.12 Millimoles per liter | Standard Deviation 2.075 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Gluc, Day 180 | -1.09 Millimoles per liter | Standard Deviation 3.045 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | K, Day 6 | 0.17 Millimoles per liter | Standard Deviation 0.384 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | K, Day 90 | 0.36 Millimoles per liter | Standard Deviation 0.477 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Na, Day 6 | 0.1 Millimoles per liter | Standard Deviation 2.82 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Cl, Day 30 | -1.6 Millimoles per liter | Standard Deviation 3.72 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Na, Day 90 | 0.4 Millimoles per liter | Standard Deviation 1.87 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Na, Day 180 | 0.5 Millimoles per liter | Standard Deviation 2.04 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Urea/BUN, Day 6 | 1.57 Millimoles per liter | Standard Deviation 2.392 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Urea/BUN, Day 30 | 1.09 Millimoles per liter | Standard Deviation 2.673 |
| Placebo | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Urea/BUN, Day 180 | 0.51 Millimoles per liter | Standard Deviation 2.364 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Urea/BUN, Day 180 | 1.04 Millimoles per liter | Standard Deviation 3.502 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Cl, Day 30 | -3.1 Millimoles per liter | Standard Deviation 5.01 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Gluc, Day 90 | -0.38 Millimoles per liter | Standard Deviation 2.17 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | K, Day 90 | 0.39 Millimoles per liter | Standard Deviation 0.404 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Na, Day 90 | -0.7 Millimoles per liter | Standard Deviation 2.91 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Gluc, Day 180 | -1.02 Millimoles per liter | Standard Deviation 2.136 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Urea/BUN, Day 30 | 2.19 Millimoles per liter | Standard Deviation 5.436 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Ca, Day 6 | 0.059 Millimoles per liter | Standard Deviation 0.1564 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | K, Day 6 | 0.21 Millimoles per liter | Standard Deviation 0.452 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Ca, Day 30 | 0.158 Millimoles per liter | Standard Deviation 0.1985 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | K, Day 30 | 0.30 Millimoles per liter | Standard Deviation 0.429 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Ca, Day 90 | 0.186 Millimoles per liter | Standard Deviation 0.196 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Na, Day 180 | -1.2 Millimoles per liter | Standard Deviation 2.9 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Ca, Day 180 | 0.182 Millimoles per liter | Standard Deviation 0.1315 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | K, Day 180 | 0.54 Millimoles per liter | Standard Deviation 0.472 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Cl, Day 6 | -1.4 Millimoles per liter | Standard Deviation 4.08 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Urea/BUN, Day 90 | 1.04 Millimoles per liter | Standard Deviation 2.655 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Cl, Day 90 | -2.7 Millimoles per liter | Standard Deviation 4.67 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Na, Day 6 | 0.0 Millimoles per liter | Standard Deviation 2.83 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Cl, Day 180 | -3.4 Millimoles per liter | Standard Deviation 3.93 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Urea/BUN, Day 6 | 1.61 Millimoles per liter | Standard Deviation 2.541 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Gluc, Day 6 | -0.35 Millimoles per liter | Standard Deviation 2.619 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Na, Day 30 | -0.8 Millimoles per liter | Standard Deviation 3.21 |
| GSK249320 15 mg/kg | Change From BL in Clinical Chemistry-urea/Blood Urea Nitrogen (BUN), Sodium (Na), Potassium (K), Glucose (Gluc), Chloride (Cl), Calcium (Ca) | Gluc, Day 30 | -0.45 Millimoles per liter | Standard Deviation 2.476 |
Secondary
Change From BL in Dexterity as Measured by Box and Blocks Test
Dexterity is ability of person to use hands skillfully in performing a task. Box and Blocks test is an objective, gross manual dexterity test in individuals with upper limb impairments. Participants were asked to move small wooden blocks from one side of a partitioned box to other. The score was determined by number of blocks transferred within a 60 second time period. Both affected and unaffected arms were tested, starting with the unaffected arm. Change from BL was calculated as the individual post- BL value minus BL value. A higher number of displaced blocks indicated a better gross dexterity and a low number of displaced blocks indicated poor gross dexterity. It was analyzed using fixed effects for treatment, visit, treatment by visit interaction, sex, age, Baseline National Institute of Health stroke scale (NIHSS) total score, BL number of blocks transferred by the affected and unaffected arms, country and presence of concomitant medications that potentially impact recovery.
Time frame: BL (Day 1), Month 1/Day 30, Month 2/Day 60, Month 3/Day 90 and Month 6/Day 180
Population: PP Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Dexterity as Measured by Box and Blocks Test | Day 30 | 10.130 Number of blocks | Standard Error 2.195 |
| Placebo | Change From BL in Dexterity as Measured by Box and Blocks Test | Day 60 | 11.469 Number of blocks | Standard Error 2.345 |
| Placebo | Change From BL in Dexterity as Measured by Box and Blocks Test | Day 90 | 15.196 Number of blocks | Standard Error 2.962 |
| Placebo | Change From BL in Dexterity as Measured by Box and Blocks Test | Day 180 | 14.869 Number of blocks | Standard Error 2.839 |
| GSK249320 15 mg/kg | Change From BL in Dexterity as Measured by Box and Blocks Test | Day 180 | 18.813 Number of blocks | Standard Error 2.11 |
| GSK249320 15 mg/kg | Change From BL in Dexterity as Measured by Box and Blocks Test | Day 30 | 12.538 Number of blocks | Standard Error 1.587 |
| GSK249320 15 mg/kg | Change From BL in Dexterity as Measured by Box and Blocks Test | Day 90 | 17.631 Number of blocks | Standard Error 1.926 |
| GSK249320 15 mg/kg | Change From BL in Dexterity as Measured by Box and Blocks Test | Day 60 | 14.484 Number of blocks | Standard Error 1.6 |
Comparison: Statistical data for Day 30. The point estimate and confidence interval are for the adjusted mean difference based on least square estimates.95% CI: [-3.067, 7.883]
Comparison: Statistical data for Day 60. The point estimate and confidence interval are for the adjusted mean difference based on least square estimates.95% CI: [-2.704, 8.735]
Comparison: Statistical data for Day 90. The point estimate and confidence interval are for the adjusted mean difference based on least square estimates.95% CI: [-4.668, 9.538]
Comparison: Statistical data for Day 180. The point estimate and confidence interval are for the adjusted mean difference based on least square estimates.95% CI: [-3.15, 11.037]
Secondary
Change From BL in ECG Parameter-Heart Rate
A single 12-lead ECG was obtained at each time point that measured heart rate. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1) Day 6, Day 30 and EW visit
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in ECG Parameter-Heart Rate | Day 6, n=60, 58 | -3.4 Beats per minute | Standard Deviation 17.57 |
| Placebo | Change From BL in ECG Parameter-Heart Rate | Day 30, n=46, 50 | -3.4 Beats per minute | Standard Deviation 19.81 |
| Placebo | Change From BL in ECG Parameter-Heart Rate | EW Visit, n=16, 16 | -5.4 Beats per minute | Standard Deviation 16.82 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameter-Heart Rate | Day 6, n=60, 58 | -4.9 Beats per minute | Standard Deviation 15.37 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameter-Heart Rate | Day 30, n=46, 50 | 0.9 Beats per minute | Standard Deviation 16 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameter-Heart Rate | EW Visit, n=16, 16 | -10.3 Beats per minute | Standard Deviation 29.58 |
Secondary
Change From BL in ECG Parameters
A single 12-lead ECG was obtained at each time point and the following ECG intervals were determined: PR, QRS, QT, RR and corrected QT (QTc), QT interval corrected by Bazett's formula (QTcB), QT interval corrected by Fridericia's formula (QTcF). BL for ECG parameters was the value of Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1), Day 6, Day 30 and EW visit
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in ECG Parameters | QT, Day 30 | 4.1 Milliseconds | Standard Deviation 43.59 |
| Placebo | Change From BL in ECG Parameters | QRS, Day 30 | 3.4 Milliseconds | Standard Deviation 10.97 |
| Placebo | Change From BL in ECG Parameters | QT, EW Visit | 20.8 Milliseconds | Standard Deviation 37.16 |
| Placebo | Change From BL in ECG Parameters | PR, EW Visit | -0.4 Milliseconds | Standard Deviation 21.01 |
| Placebo | Change From BL in ECG Parameters | QTc, Day 6 | 2.9 Milliseconds | Standard Deviation 30.7 |
| Placebo | Change From BL in ECG Parameters | QRS, EW Visit | 2.6 Milliseconds | Standard Deviation 27.47 |
| Placebo | Change From BL in ECG Parameters | QTc, Day 30 | -1.3 Milliseconds | Standard Deviation 32.92 |
| Placebo | Change From BL in ECG Parameters | QTcB, Day 6 | 2.2 Milliseconds | Standard Deviation 124.73 |
| Placebo | Change From BL in ECG Parameters | QTc, EW Visit | 7.1 Milliseconds | Standard Deviation 27.75 |
| Placebo | Change From BL in ECG Parameters | RR, Day 6 | 61.1 Milliseconds | Standard Deviation 246.84 |
| Placebo | Change From BL in ECG Parameters | QRS, Day 6 | 4.9 Milliseconds | Standard Deviation 15.75 |
| Placebo | Change From BL in ECG Parameters | QTcB, Day 30 | -31.9 Milliseconds | Standard Deviation 120.26 |
| Placebo | Change From BL in ECG Parameters | RR, EW Visit | -21.6 Milliseconds | Standard Deviation 164.19 |
| Placebo | Change From BL in ECG Parameters | QTcB, EW Visit | 28.2 Milliseconds | Standard Deviation 37.06 |
| Placebo | Change From BL in ECG Parameters | PR, Day 6 | -1.0 Milliseconds | Standard Deviation 30.47 |
| Placebo | Change From BL in ECG Parameters | QTcF, Day 6 | 4.3 Milliseconds | Standard Deviation 74.12 |
| Placebo | Change From BL in ECG Parameters | QT, Day 6 | 10.4 Milliseconds | Standard Deviation 40.86 |
| Placebo | Change From BL in ECG Parameters | QTcF, Day 30 | -16.9 Milliseconds | Standard Deviation 75.41 |
| Placebo | Change From BL in ECG Parameters | RR, Day 30 | 80.5 Milliseconds | Standard Deviation 245.31 |
| Placebo | Change From BL in ECG Parameters | QTcF, EW Visit | 26.0 Milliseconds | Standard Deviation 31.85 |
| Placebo | Change From BL in ECG Parameters | PR, Day 30 | -5.9 Milliseconds | Standard Deviation 36.05 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTcF, EW Visit | 18.3 Milliseconds | Standard Deviation 62.78 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | PR, Day 30 | -3.5 Milliseconds | Standard Deviation 42.08 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | PR, Day 6 | -0.8 Milliseconds | Standard Deviation 20.02 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | PR, EW Visit | 3.1 Milliseconds | Standard Deviation 33.96 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QRS, Day 6 | -4.0 Milliseconds | Standard Deviation 44.11 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | RR, Day 6 | 12.9 Milliseconds | Standard Deviation 154.09 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QRS, Day 30 | 1.1 Milliseconds | Standard Deviation 17.74 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QRS, EW Visit | -23.7 Milliseconds | Standard Deviation 81.24 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | RR, Day 30 | -21.8 Milliseconds | Standard Deviation 181.99 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | RR, EW Visit | 85.6 Milliseconds | Standard Deviation 349.82 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QT, Day 6 | 9.4 Milliseconds | Standard Deviation 36.46 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QT, Day 30 | -12.1 Milliseconds | Standard Deviation 42.06 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QT, EW Visit | 43.7 Milliseconds | Standard Deviation 93.85 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTc, Day 6 | 6.8 Milliseconds | Standard Deviation 43.87 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTc, Day 30 | -2.2 Milliseconds | Standard Deviation 39.49 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTc, EW Visit | 8.9 Milliseconds | Standard Deviation 69.58 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTcB, Day 6 | 4.5 Milliseconds | Standard Deviation 46.49 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTcB, Day 30 | -13.9 Milliseconds | Standard Deviation 79.33 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTcB, EW Visit | 6.9 Milliseconds | Standard Deviation 52.02 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTcF, Day 6 | 5.7 Milliseconds | Standard Deviation 33.25 |
| GSK249320 15 mg/kg | Change From BL in ECG Parameters | QTcF, Day 30 | -12.0 Milliseconds | Standard Deviation 58.16 |
Secondary
Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count
EOS, LYM, Total ANC, PLT count and WBC count were measured at BL, Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value.By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | Total ANC, Day 30 | -1.486 Giga (10^9 cells) per liter | Standard Deviation 2.4578 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | PLT Count, Day 30 | 40.5 Giga (10^9 cells) per liter | Standard Deviation 62.89 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | WBC Count,Day 6 | -0.40 Giga (10^9 cells) per liter | Standard Deviation 2.294 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | WBC Count, Day 180 | -2.15 Giga (10^9 cells) per liter | Standard Deviation 2.496 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | EOS, Day 6 | 0.049 Giga (10^9 cells) per liter | Standard Deviation 0.1153 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | EOS, Day 30 | 0.058 Giga (10^9 cells) per liter | Standard Deviation 0.2207 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | EOS, Day 90 | 0.058 Giga (10^9 cells) per liter | Standard Deviation 0.1175 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | EOS, Day 180 | 0.045 Giga (10^9 cells) per liter | Standard Deviation 0.1314 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | LYM, Day 6 | -0.046 Giga (10^9 cells) per liter | Standard Deviation 0.3904 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | LYM, Day 30 | 0.026 Giga (10^9 cells) per liter | Standard Deviation 0.4666 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | LYM, Day 90 | 0.066 Giga (10^9 cells) per liter | Standard Deviation 0.411 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | LYM, Day 180 | 0.017 Giga (10^9 cells) per liter | Standard Deviation 0.5005 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | Total ANC, Day 6 | -0.375 Giga (10^9 cells) per liter | Standard Deviation 2.2795 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | Total ANC, Day 90 | -1.469 Giga (10^9 cells) per liter | Standard Deviation 2.1498 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | Total ANC, Day 180 | -2.202 Giga (10^9 cells) per liter | Standard Deviation 2.7396 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | PLT Count, Day 6 | 17.4 Giga (10^9 cells) per liter | Standard Deviation 37.57 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | PLT Count, Day 90 | 33.2 Giga (10^9 cells) per liter | Standard Deviation 53.36 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | PLT Count, Day 180 | 19.9 Giga (10^9 cells) per liter | Standard Deviation 35.91 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | WBC Count, Day 30 | -1.46 Giga (10^9 cells) per liter | Standard Deviation 2.524 |
| Placebo | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | WBC Count, Day 90 | -1.45 Giga (10^9 cells) per liter | Standard Deviation 2.017 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | LYM, Day 90 | 0.236 Giga (10^9 cells) per liter | Standard Deviation 0.5854 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | PLT Count, Day 6 | 32.4 Giga (10^9 cells) per liter | Standard Deviation 41.01 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | PLT Count, Day 180 | 35.9 Giga (10^9 cells) per liter | Standard Deviation 39.15 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | LYM, Day 180 | 0.075 Giga (10^9 cells) per liter | Standard Deviation 0.5919 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | WBC Count, Day 90 | -1.28 Giga (10^9 cells) per liter | Standard Deviation 2.119 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | PLT Count, Day 30 | 47.6 Giga (10^9 cells) per liter | Standard Deviation 44.23 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | WBC Count, Day 180 | -0.55 Giga (10^9 cells) per liter | Standard Deviation 1.943 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | Total ANC, Day 6 | -0.756 Giga (10^9 cells) per liter | Standard Deviation 2.5842 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | EOS, Day 6 | 0.082 Giga (10^9 cells) per liter | Standard Deviation 0.1692 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | Total ANC, Day 30 | -0.581 Giga (10^9 cells) per liter | Standard Deviation 4.7282 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | EOS, Day 30 | 0.086 Giga (10^9 cells) per liter | Standard Deviation 0.1318 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | WBC Count,Day 6 | -0.78 Giga (10^9 cells) per liter | Standard Deviation 2.288 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | EOS, Day 90 | 0.058 Giga (10^9 cells) per liter | Standard Deviation 0.1149 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | Total ANC, Day 90 | -1.455 Giga (10^9 cells) per liter | Standard Deviation 2.3515 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | EOS, Day 180 | 0.048 Giga (10^9 cells) per liter | Standard Deviation 0.1206 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | PLT Count, Day 90 | 60.4 Giga (10^9 cells) per liter | Standard Deviation 56.3 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | LYM, Day 6 | -0.030 Giga (10^9 cells) per liter | Standard Deviation 0.675 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | Total ANC, Day 180 | -0.579 Giga (10^9 cells) per liter | Standard Deviation 1.6956 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | LYM, Day 30 | -0.002 Giga (10^9 cells) per liter | Standard Deviation 0.5728 |
| GSK249320 15 mg/kg | Change From BL in Eosinophils (EOS), Lymphocytes (LYM), Total Absolute Neutrophil Count (ANC), Platelet (PLT) Count, White Blood Cell (WBC) Count | WBC Count, Day 30 | -0.54 Giga (10^9 cells) per liter | Standard Deviation 4.819 |
Secondary
Change From BL in Hematology- Hemoglobin
Hemoglobin was measured at BL Day 6, Day 30, Day 90 and Day 180. BL was the value obtained on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. . By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Hematology- Hemoglobin | Day 6 | -0.1 Grams per liter | Standard Deviation 9.55 |
| Placebo | Change From BL in Hematology- Hemoglobin | Day 30 | -1.0 Grams per liter | Standard Deviation 13.19 |
| Placebo | Change From BL in Hematology- Hemoglobin | Day 90 | -4.1 Grams per liter | Standard Deviation 16.61 |
| Placebo | Change From BL in Hematology- Hemoglobin | Day 180 | -6.2 Grams per liter | Standard Deviation 17.7 |
| GSK249320 15 mg/kg | Change From BL in Hematology- Hemoglobin | Day 180 | 7.6 Grams per liter | Standard Deviation 13.45 |
| GSK249320 15 mg/kg | Change From BL in Hematology- Hemoglobin | Day 6 | 2.4 Grams per liter | Standard Deviation 10.21 |
| GSK249320 15 mg/kg | Change From BL in Hematology- Hemoglobin | Day 90 | 4.7 Grams per liter | Standard Deviation 15.91 |
| GSK249320 15 mg/kg | Change From BL in Hematology- Hemoglobin | Day 30 | 3.8 Grams per liter | Standard Deviation 14.84 |
Secondary
Change From BL in NIHSS Total Score
The NIHSS is a 15 item, standardized, disease-specific, deficit scale which measures neurological impairment (level of consciousness, eye movements, visual fields, facial symmetry, motor strength (arm and leg), coordination, sensation, language (aphasia and dysarthria), and neglect) and is used to quantify participant status by measuring the severity of the stroke as assessed by NIHSS certified study personnel. The total NIHSS score is calculated as the sum of responses to the 15 items. The total NIHSS score ranges from 0-42, with a higher score indicative of a more severe impairment. By-visit sample sizes vary due to missing data or early termination of the study. Change from BL was calculated as the individual post-Baseline value minus the BL value. BL was defined as the value at Day 1.
Time frame: BL (Day 1), Day 30, Day 90 and Day 180
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in NIHSS Total Score | Day 1 | 10.0 Scores on a scale | Standard Deviation 4.4 |
| Placebo | Change From BL in NIHSS Total Score | Day 90 | 5.0 Scores on a scale | Standard Deviation 3.83 |
| Placebo | Change From BL in NIHSS Total Score | Day 30 | 6.4 Scores on a scale | Standard Deviation 4.4 |
| Placebo | Change From BL in NIHSS Total Score | Day 180 | 3.9 Scores on a scale | Standard Deviation 3.22 |
| GSK249320 15 mg/kg | Change From BL in NIHSS Total Score | Day 180 | 4.2 Scores on a scale | Standard Deviation 3.87 |
| GSK249320 15 mg/kg | Change From BL in NIHSS Total Score | Day 1 | 9.8 Scores on a scale | Standard Deviation 3.79 |
| GSK249320 15 mg/kg | Change From BL in NIHSS Total Score | Day 30 | 5.7 Scores on a scale | Standard Deviation 4.66 |
| GSK249320 15 mg/kg | Change From BL in NIHSS Total Score | Day 90 | 4.8 Scores on a scale | Standard Deviation 4.89 |
Secondary
Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Safety was measured by monitoring vital signs including blood pressure. The BL for DBP and SBP was the value of pre-dose assessment on Day 1. Change from BL was calculated as the individual post-Baseline value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study.
Time frame: BL (Day 1) , Day 6, Day 180 and early withdrawal (EW) visit
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, EW visit | -15.2 Millimeters of mercury | Standard Deviation 29.08 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 6 Post-dose | 2.4 Millimeters of mercury | Standard Deviation 15.06 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 180 | -6.4 Millimeters of mercury | Standard Deviation 22.96 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 180 | 8.1 Millimeters of mercury | Standard Deviation 13.97 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1 Post-dose | 1.7 Millimeters of mercury | Standard Deviation 10.58 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, EW visit | -5.0 Millimeters of mercury | Standard Deviation 15.55 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 6 Post-dose | -0.9 Millimeters of mercury | Standard Deviation 24.59 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1 Post-dose | 3.1 Millimeters of mercury | Standard Deviation 16.15 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 6 Pre-dose | 0.2 Millimeters of mercury | Standard Deviation 16.52 |
| Placebo | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 6 Pre-dose | -3.5 Millimeters of mercury | Standard Deviation 26.46 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 6 Pre-dose | -1.1 Millimeters of mercury | Standard Deviation 11.98 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 6 Post-dose | -2.0 Millimeters of mercury | Standard Deviation 20.14 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 180 | -6.4 Millimeters of mercury | Standard Deviation 27.79 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, EW visit | -0.0 Millimeters of mercury | Standard Deviation 25.42 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1 Post-dose | 0.5 Millimeters of mercury | Standard Deviation 10.14 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 6 Pre-dose | -6.0 Millimeters of mercury | Standard Deviation 20.13 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 6 Post-dose | 1.9 Millimeters of mercury | Standard Deviation 16.36 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 180 | 5.0 Millimeters of mercury | Standard Deviation 14.6 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, EW visit | 1.8 Millimeters of mercury | Standard Deviation 15.05 |
| GSK249320 15 mg/kg | Change From BL in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1 Post-dose | 0.7 Millimeters of mercury | Standard Deviation 11.81 |
Secondary
Change From BL in Vitals Signs-Heart Rate
Safety was measured by monitoring vital signs including heart rate. The BL for heart rate was the value of pre-dose assessment on Day 1. Change from BL was calculated as the individual post-BL value minus the BL value. By-visit sample sizes vary due to missing data or early termination of the study. BL was defined as Day 1.
Time frame: Day 1, Day 6, Day 180 and EW visit
Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From BL in Vitals Signs-Heart Rate | Day 6 Pre-dose | -1.8 Beats per minute | Standard Deviation 13.03 |
| Placebo | Change From BL in Vitals Signs-Heart Rate | Day 180 | -0.3 Beats per minute | Standard Deviation 17.5 |
| Placebo | Change From BL in Vitals Signs-Heart Rate | Day 1 Post-dose | 0.9 Beats per minute | Standard Deviation 8.68 |
| Placebo | Change From BL in Vitals Signs-Heart Rate | EW visit | 3.3 Beats per minute | Standard Deviation 15.47 |
| Placebo | Change From BL in Vitals Signs-Heart Rate | Day 6 Post-dose | -3.9 Beats per minute | Standard Deviation 12.09 |
| GSK249320 15 mg/kg | Change From BL in Vitals Signs-Heart Rate | EW visit | -2.1 Beats per minute | Standard Deviation 15.4 |
| GSK249320 15 mg/kg | Change From BL in Vitals Signs-Heart Rate | Day 1 Post-dose | 0.7 Beats per minute | Standard Deviation 7.98 |
| GSK249320 15 mg/kg | Change From BL in Vitals Signs-Heart Rate | Day 6 Pre-dose | -0.4 Beats per minute | Standard Deviation 17.47 |
| GSK249320 15 mg/kg | Change From BL in Vitals Signs-Heart Rate | Day 6 Post-dose | -3.1 Beats per minute | Standard Deviation 15.3 |
| GSK249320 15 mg/kg | Change From BL in Vitals Signs-Heart Rate | Day 180 | -3.0 Beats per minute | Standard Deviation 15.48 |
Secondary
Clearance (CL) for GSK249320
Blood samples were collected for determination of plasma concentrations of GSK249320. CL was derived from the plasma concentration-time data. Analysis was performed for PK Population that comprised of all participants in the Safety Population who had at least one PK sample with a concentration above the non-quantifiable limit. Only participants in the GSK249320 15 mg/kg group were analyzed.
Time frame: Up to Day 180
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Clearance (CL) for GSK249320 | 0.1243 Milligrams/kilograms/hour | Geometric Coefficient of Variation 20.4 |
Secondary
Maximum Observed Plasma Concentration (Cmax) for GSK249320
Cmax is the maximum observed concentration of GSK249320 obtained at the end of infusion post dose on Day 6. Due to early termination of the study, this data was not collected.
Time frame: Pre-dose and post-dose up to Day 180
Population: The Pharmacokinetics (PK) population consisted of all participants in the Safety population who have at least one PK sample with a concentration above the non-quantifiable limit. Data not collected due to early termination of study.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Maximum Observed Plasma Concentration (Cmax) for GSK249320 | Day 6 | — |
| Unknown | Maximum Observed Plasma Concentration (Cmax) for GSK249320 | Day 30 | — |
| Unknown | Maximum Observed Plasma Concentration (Cmax) for GSK249320 | Day 180 | — |
Secondary
Mean Change From BL to Month 6/ Day 180 in Gait Velocity
Gait is the way or manner in which a person walks. Gait velocity (walking speed) is an objective, quantitative measure of lower extremity motor recovery in individuals who have had a stroke. Participants were asked to walk at their usual pace over a level, indoor 10 m distance and were allowed to use their normal assistive devices. The time (s) taken by the participants to travel the 10 m distance was recorded. Gait velocity (m/s) as assessed by study personnel was derived as: 10 divided by time to walk 10 m. Two trials of gait velocity were conducted at each time point. Change from BL was calculated as the mean Month 3/Day 90 value minus the mean BL value. BL was defined as Day 1. The measure type displayed are posterior means.
Time frame: BL (Day 1) and Month 6/Day 180
Population: ITT Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From BL to Month 6/ Day 180 in Gait Velocity | 0.5442 m/s | Standard Deviation 0.0665 |
| GSK249320 15 mg/kg | Mean Change From BL to Month 6/ Day 180 in Gait Velocity | 0.6236 m/s | Standard Deviation 0.0556 |
Comparison: Credible intervals are displayed as confidence intervals. Posterior means, standard deviations, and credible intervals are provided in the table.p-value: 0.82895% CI: [-0.093, 0.247]Bayesian method
Secondary
Number of Falls Over Time
The number of participants who experienced 1, 2, 3 or \>=4 falls between BL to Day 90 and BL to Day 180 is summarized. By-visit sample sizes vary due to missing data or early termination of the study. The participants who experienced atleast one-fall were reported
Time frame: BL (Day 1), Day 90 and Day 180
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Falls Over Time | Baseline to Day 90, 2 Falls | 3 Participants |
| Placebo | Number of Falls Over Time | Baseline to Day 90, 1 Fall | 8 Participants |
| Placebo | Number of Falls Over Time | Baseline to Day 90, 3 Falls | 0 Participants |
| Placebo | Number of Falls Over Time | Baseline to Day 90, >=4 Falls | 4 Participants |
| Placebo | Number of Falls Over Time | Baseline to Day 180, 1 Fall | 7 Participants |
| Placebo | Number of Falls Over Time | Baseline to Day 180, 2 Falls | 6 Participants |
| Placebo | Number of Falls Over Time | Baseline to Day 180, 3 Falls | 1 Participants |
| Placebo | Number of Falls Over Time | Baseline to Day 180, >=4 Falls | 4 Participants |
| GSK249320 15 mg/kg | Number of Falls Over Time | Baseline to Day 90, >=4 Falls | 1 Participants |
| GSK249320 15 mg/kg | Number of Falls Over Time | Baseline to Day 180, >=4 Falls | 3 Participants |
| GSK249320 15 mg/kg | Number of Falls Over Time | Baseline to Day 180, 2 Falls | 2 Participants |
| GSK249320 15 mg/kg | Number of Falls Over Time | Baseline to Day 90, 1 Fall | 6 Participants |
| GSK249320 15 mg/kg | Number of Falls Over Time | Baseline to Day 90, 2 Falls | 3 Participants |
| GSK249320 15 mg/kg | Number of Falls Over Time | Baseline to Day 180, 1 Fall | 9 Participants |
| GSK249320 15 mg/kg | Number of Falls Over Time | Baseline to Day 90, 3 Falls | 2 Participants |
| GSK249320 15 mg/kg | Number of Falls Over Time | Baseline to Day 180, 3 Falls | 2 Participants |
Secondary
Number of Participants Experiencing Falls
The number of participants who experienced at least one fall between BL to Day 90 and BL to Day 180 is summarized.
Time frame: BL (Day 1) Day 90 and Day 180
Population: Safety population is defined as participants who had received at least one infusion of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Experiencing Falls | Baseline to Day 90 | 15 Participants |
| Placebo | Number of Participants Experiencing Falls | Baseline to Day 180 | 18 Participants |
| GSK249320 15 mg/kg | Number of Participants Experiencing Falls | Baseline to Day 90 | 12 Participants |
| GSK249320 15 mg/kg | Number of Participants Experiencing Falls | Baseline to Day 180 | 16 Participants |
Secondary
Number of Participants With Events Common to Stroke
Events common to stroke were those events that commonly occurred after a stroke and are generally associated with the underlying stroke or the progression of stroke. These included joint or soft tissue pain, bladder incontinence, depression/mood disorder, urinary tract infection, dysphagia, bowel incontinence, dysarthia, confusion, spasticity, limb edema, aspiration pneumonia, hemorrhagic transformation (symptomatic or asymptomatic), pressure ulcers, progression of stroke, malnutrition, deep vein thrombosis, brain herniation, pulmonary embolism, seizures, and falls.
Time frame: From Day 1 until early withdrawal, death, Month 6/Day 180
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Events Common to Stroke | Depression/Mood Disorder | 17 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Aspiration Pneumonia | 5 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Urinary tract infection | 17 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Confusion | 8 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Pressure Ulcers | 3 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Hemorrhagic Transformation | 4 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Progression of Stroke | 2 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Bowel Incontinence | 11 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Malnutrition | 1 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Joint or soft tissue pain | 19 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Deep vein thrombosis | 2 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Dysphagia | 12 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Brain Herniation | 0 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Bladder Incontinence | 11 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Pulmonary embolism | 1 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Spasticity | 9 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Seizures | 0 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Dysarthia | 11 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Falls | 18 Participants |
| Placebo | Number of Participants With Events Common to Stroke | Limb edema | 5 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Falls | 16 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Joint or soft tissue pain | 22 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Bladder Incontinence | 23 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Urinary tract infection | 13 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Dysphagia | 12 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Bowel Incontinence | 12 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Dysarthia | 11 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Confusion | 13 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Spasticity | 9 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Limb edema | 12 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Aspiration Pneumonia | 3 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Hemorrhagic Transformation | 4 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Pressure Ulcers | 2 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Progression of Stroke | 2 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Malnutrition | 2 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Deep vein thrombosis | 0 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Brain Herniation | 1 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Pulmonary embolism | 0 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Seizures | 1 Participants |
| GSK249320 15 mg/kg | Number of Participants With Events Common to Stroke | Depression/Mood Disorder | 16 Participants |
Secondary
Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points
Participants were categorized at each visit into the following gait velocity categories: 0 m/s, \>0 to \<0.4 m/s, \>=0.4 m/s to 0.8 m/s and \>0.8m/s. A distinction was made between participants who are too incapacitated to walk (i.e., gait velocity = 0m/s) and participants for whom the gait velocity assessment was not performed due to another reason (i.e., truly missing data). Participants were asked to walk at their usual or normal pace and using their normal assistive devices. Two trials of gait velocity were conducted at each time point. The number of participants transitioning from one gait velocity category to another category was assessed at each post-Baseline visit and was presented in terms of the following transition categories: worsened, no change, improved 1 level, improved 2 levels and improved 3 levels. By-visit sample sizes vary due to missing data or early termination of the study, missing data was not imputed.
Time frame: BL (Day 1), Month 1/Day 30, Month 2/Day 60, Month 3/Day 90 and Month 6/Day 180.
Population: PP Population consisted of all participants who were included in the ITT population and did not violate protocol with regards to inclusion/exclusion criteria, unblinding, investigational product administration and gait velocity assessments. Only participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, Worsened | 1 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, No Change | 19 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, Improved 1 Levels | 11 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, Improved 2 Levels | 9 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, Improved 3 Levels | 8 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, Worsened | 0 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, No Change | 13 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, Improved 1 Level | 14 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, Improved 2 Levels | 6 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, Improved 3 Levels | 9 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, Worsened | 1 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, No Change | 9 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, Improved 1 Level | 12 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, Improved 2 Levels | 10 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, Improved 3 Levels | 10 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, Worsened | 1 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, No Change | 7 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, Improved 1 Level | 9 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, Improved 2 Levels | 11 Participants |
| Placebo | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, Improved 3 Levels | 8 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, Improved 1 Level | 14 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, Worsened | 0 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, Worsened | 0 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, No Change | 18 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, Worsened | 0 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, Improved 1 Levels | 11 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, No Change | 8 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, Improved 2 Levels | 9 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, Improved 3 Levels | 14 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 30, Improved 3 Levels | 11 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, Improved 1 Level | 14 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, Worsened | 0 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, No Change | 6 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, No Change | 14 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, Improved 2 Levels | 7 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, Improved 1 Level | 11 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 180, Improved 2 Levels | 5 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, Improved 2 Levels | 7 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 90, Improved 3 Levels | 12 Participants |
| GSK249320 15 mg/kg | Number of Participants With Indicated Transition From One Gait Velocity Category to Another Category at the Indicated Time Points | Day 60, Improved 3 Levels | 10 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs)
An AE is 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. A SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect or all events of possible drug-induced liver injury with hyperbilirubinaemia. Medical or scientific judgment is exercised in other situations.
Time frame: Up to 14 months
Population: Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Any AE | 57 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Any SAE | 16 Participants |
| GSK249320 15 mg/kg | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Any AE | 49 Participants |
| GSK249320 15 mg/kg | Number of Participants With Serious Adverse Events (SAEs) and Adverse Events (AEs) | Any SAE | 9 Participants |
Secondary
Number of Participants With Suicidal Ideation Via Columbia Suicide Severity Rating Scale (CSSRS)
C-SSRS is a clinician-rated scale that evaluates severity and change of suicidality by integrating both suicidality behavior and ideation. For Suicidal Ideation (SI), participants were scored non-suicidal:0, wish to be dead:1, non-specific active suicidal thoughts:2, active suicidal ideation with associated thoughts of methods without intent:3, active suicidal ideation with some intent to act on suicidal thoughts without clear plan:4, active suicidal ideation with plan and intent:5 (most severe). SI intensity total score was the sum of suicidal ideation severity rating scores for frequency, duration, controllability, deterrents, and reasons for ideation. For each item, each participant got an intensity score from 0(none) to 5(worst). Therefore, the suicidal ideation intensity total score range from 0 to 25, with a score of 0 given for no suicidal ideation.
Time frame: Da y 1, Da y 6, Day 30, Day 60, Day 90 and Day 180
Population: Safety Population. Number of participants with at least one on-treatment C-SSRS assessment were included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Suicidal Ideation Via Columbia Suicide Severity Rating Scale (CSSRS) | 10 Participants |
| GSK249320 15 mg/kg | Number of Participants With Suicidal Ideation Via Columbia Suicide Severity Rating Scale (CSSRS) | 3 Participants |
Secondary
PK as Measured by Plasma Decay Half-life (t1/2) GSK249320
Blood samples were collected for determination of plasma concentrations of GSK249320. Terminal phase half-life was derived from the plasma concentration-time data. Only participants in the GSK249320 15 mg/kg group were analyzed.
Time frame: Up to Day 180
Population: PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | PK as Measured by Plasma Decay Half-life (t1/2) GSK249320 | 23.09 Days |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) GSK249320
Tmax is the time of the occurrence of Cmax. The Cmax is defined as the maximum observed concentration of GSK249320 obtained at the end of infusion post dose on day 6. Due to early termination of the study data for Tmax was not collected.
Time frame: Pre-dose and post-dose up to Day 180
Population: PK population. Due to early termination of the study, data for Tmax was not collected
Secondary
Volume of Distribution (V1 and V2) and Volume at Steady State (Vss) for GSK249320
Blood samples were collected for determination of plasma concentrations of GSK249320. V1, V2 and Vss were derived from the plasma concentration-time data. Analysis was performed for PK Population that comprised of all participants in the Safety Population who had at least one PK sample with a concentration above the non-quantifiable limit. Only participants in the GSK249320 15 mg/kg group were analyzed.
Time frame: Up to Day 180
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Volume of Distribution (V1 and V2) and Volume at Steady State (Vss) for GSK249320 | Vss | 85.2892 milliliters/kilogram | Geometric Coefficient of Variation 11.5 |
| Placebo | Volume of Distribution (V1 and V2) and Volume at Steady State (Vss) for GSK249320 | V1 | 43.6992 milliliters/kilogram | Geometric Coefficient of Variation 6.7 |
| Placebo | Volume of Distribution (V1 and V2) and Volume at Steady State (Vss) for GSK249320 | V2 | 41.4193 milliliters/kilogram | Geometric Coefficient of Variation 17.8 |