Safety Escalating Repeat IV, in Stroke Patients
Condition: Ischaemic Attack, Transient
MeSH terms: Ischemic Attack, Transient
Intervention: GSK249320; PLACEBO
Intervention description: I.V. infusion; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No

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

Eligibility criteria:

        Inclusion Criteria:

          -  Have a confirmed diagnosis of stroke

          -  Stroke onset must be within the last 24-72 hours.

          -  Have a stroke that is either:

          -  radiologically confirmed to be ischaemic and supratentorial. The diameter of the
             ischemic lesion is >15mm in any singlle direction or the volume is >4cc. OR

          -  radiologically confirmed to be an intracerebral hemorrhage that is supratentorial,
             deep (i.e., blood must not directly contact cerebral cortex) and with minimal or no
             intraventricular extension. The Intracerebral Hemorrahage (CH) score must be 0-2 and
             is calculated based on age, Galsgow coma Scale score ad the initial CT or MRI findings
             for the index stroke. See the SOM for the full calculation procedure.

          -  Have a total NIHSS score of 3-21.

          -  Have an upper and/or lower limb deficit defined as:

          -  Score of 1-3 on the NIHSS Motor Arm question, and palpable and observable voluntary
             extension or flexion of the fingers. AND/OR b. Score of 1-3 on the NIHSS Motor Leg
             question

          -  Aged 18-90, inclusive.

          -  Male subjects and females of non-child-bearing potential are allowed to participate in
             this study.

          -  Females of child-bearing potential are also allowed to participate in this study
             provided they are using a contraceptive method with a failure rate of <1%.

        Exclusion Criteria:

          -  History of a previous symptomatic stroke within 3 months prior to study entry.

          -  Presence of significant disability prior to the current stroke. Significant disability
             is defined as having a pre-stroke Rankin score of >2.

          -  Presence of depression that is active and not adequately controlled such that it
             interferred with major activities of daily living immediately prior to the current
             stroke.

          -  Subjects who are not alert or are unresponsive as defined by a score of 2 or 3 on the
             NIHSS Level of Consciousness question (question #1a).

          -  Presence of significant aphasia as likely to confound or interfere with completion of
             the study assessments.

          -  Presence of peripheral neuropathy, including diabetic neuropathy, which is clinically
             active and symptomatic at time of screening.

          -  Presence of neurological or psychiatric disease, such as dementia or mild cognitive
             impairment, prior to study entry that is likely to confound clinical evaluations.

          -  Presence of a demyelinating disease, such as multiple sclerosis.

          -  Evidence of other chronic co-morbid conditions or unstable acute systemic illnesses
             which, in the opinion of the investigator, could shorten the subject's survival or
             limit his/her ability to complete the study.

          -  History of sensitivity to heparin or heparin-induced thrombocytopenia.

          -  Presence of QTcB > 500 msec; or uncorrected QT >600msec (machine or manual over-read)
             on baseline ECG.

          -  Contraindication to TMS, such as:

          -  have metal present, such as hardware or plate on the scalp in the area to which TMS
             will be applied, implanted cardiac pacemaker, implanted prosthetic heart valve,
             medication pump or line, metallic implant or clip in the head/neck, electrical,
             mechanical or magnetic implants, neuro-stimulation device, or orthodontic work
             involving ferromagnetic materials

          -  occupation or activity that may cause accidental lodging of ferromagnetic materials or
             embedded metal fragments in the head. Subjects can be cleared by a head computed
             tomography scan.

          -  concomitant use of drugs that substantially lower seizure threshold (e.g., tricyclic
             antidepressants and neuroleptics)

          -  known history of seizures or epilepsy

          -  brain tumor, recent brain injury (within 5 years) associated with definite loss of
             consciousness, or any history of brain surgery

          -  Contraindication to MRI, such as:

          -  have metal present, such as implanted cardiac pacemaker, implanted prosthetic heart
             valve, medication pump or line, metallic implant or clip in the head/neck, electrical,
             mechanical or magnetic implants, neuro-stimulation device, or orthodontic work
             involving ferromagnetic materials, permanent tattooed metallic eye-liner

          -  occupation or activity that may cause accidental lodging of ferromagnetic materials or
             embedded metal fragments in the head. Subjects can be cleared by a head computed
             tomography scan.

          -  claustrophobia

          -  Participation in any investigational rehabilitation paradigm targeting stroke recovery
             during the duration of this study.

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

        Pregnant or lactating females.

          -  Subjects considered unwilling or unable to comply with the procedures and study visit
             schedule outlined in the protocol.