GAIN Study (Phase III GV Study)
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þ Inclusion:
 - Age more than 18 years
 - Diagnosed with acute stroke (hemorrhagic or ischemic)
 - Has limb weakness
 - Previously independent
 - Onset less than 6 hours ago

GV STROKE STUDY FACT SHEET (Phase II)
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Study Name: A Multicenter, Randomized, Double-blind, Placebo-controlled Study
to Examine the Safety and Pharmacokinetics of an Intravenous Infusion Regimen
with a Loading Dose (800 mg) and Five Maintenance Doses (200 mg- each) of GV1
50526 in the Treatment of Patientswith a Clinical Diagnosis of Acute Stroke
    
    Background: Acute ischemic stroke accounts for 85% of all strokes. A new
classification of drugs called neuroprotectors are being tested for acute
ischernic stroke. This protocol is designed to test the safety of GV150526,
an experimental intravenous therapy in the early stages of development that
may limit evolution of the infarct following acute ischemic stroke.
GV150526 is a potent antagonist at the glycine site of the N-Methyl-D-aspartate
(NMDA) receptor. It is not FDA approved except for use in stroke research.
    
Design: This is a Phase-11 multi-center, double-blind, randomized (2 active: 1
placebo), placebo controlled, single dose regimen trial. The study %*All be
conducted at approximately 40 hospital centers throughout the US and Canada.
Up to 20 patients YAII be enrolled at this site.

Study population,
Inclusion criteria:
     1) Symptoms consistent with acute stroke.
     2) Symptoms should be present at the time of study drug administration.
     3) Treatment initiated %vithin 12 hours of onset of symptoms. For
        patients who awake with deficits, the time of onset is defined as the
        time at which they were last known to be symptom- free.
     4) >18 years of age
     5) No previous significant functional disability, defined as a
        Modified Rankin score of <1 prior to stroke onset. 6) Written informed
        consent has been obtained
    
Exclusion criteria:
     1) Patients who are not alert, requiring repeated stimulation to attend;
        or obtunded, requiring strong or painful stimulation to make movements
        (not stereotyped) or responding only writh reflex motor or autonomic
        effects, or totally unresponsive, flaccid, areflexic
     2) Neurologic or psychiatric impairment prior to entry
     3) Diagnosis of subarachnoid hemorrhage.
     4) Prior medical history of epilepsy
     5) Patients presenting only with sensory loss, dysarthria or facial
        weakness
     6) Seizure at onset of heurological deficit
     7) History of stroke vAthin three months prior to study entry
     8) Symptoms consistent with acute myocardial infarction
     9) Symptoms consistent with severe congestive heart failure (NYHA Class
        III/IV)
     10) Known history of liver disease
     11) Known history of renal impairment
     12) Clinical picture consistent with malignant hypertension
     13) Treatment with aspirin (>1 gm) within 24 hour prior to randomization
     14) Evidence of other chronic co-morbid conditions or unstable acute
         systemic illness which, in the opinion of the investigator, could
         shorten the patient's survival or limit the ability to complete the
         study
     15) Women who are pregnant or lactating.
     16) Treatment with an investigational drug or device within the past
         three months
     17) Previous exposure to GV150526 in this trial or in another trial
     18) Patients considered unable to unwilling to comply with the protocol
    
Specific Procedures
      The study consists of a 4 hour intravenous infusion of the study drug
(800 mg GV1 50526 in 500 cc 5% Dextrose) or placebo, followed by 5 maintenance
doses (200 mg GV150526) to be given every 12 hours for 3 days. The patient is
then reexamined in 1 and 4 weeks after enrollment into the study.
    
Risks Involved
    The most frequent side effects reported by healthy volunteers receiving
this study drug were headache, sleepiness, and irritation or coldness at the
site where drug was infusing. When patients received a hig-Wr dose of GVI
50526 than will be used in this study, a change in bilirubin was seen in some
patients. The bilirubin tended to return to normal after GV150526 was stopped.
Because GV150526 is still an experimental drug in the early stages of
development, there may be side effects that are unknown at this time. The
patient will be medically treated for any adverse event by the medical staff
as needed.
    
Questions? Please call Dr. Gregory Larkin (principal investigator) at x5772 or
pager 1582, Susan Mathias, CRNP (Stroke Study Coordinator) at x5827 or pager
1065, or contact the DEM Stroke MD/RN on call (24 hour call) x 8222.