A Study to Evaluate the Efficacy and Safety of TF0023 Spray on Subjects With Ischemic Strokes

Exclusion Criteria

• •1. Pregnant or lactating female.
• •2. Any condition, including any significant medical or neuropsychiatric condition, including the presence of laboratory abnormalities, which in the judgment of the investigator places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study including, but not limited to:
• •* Aspartate transaminase (AST) or alanine transaminase (ALT) \>3 × the upper limit of normal (ULN) at screening.
• •* Serum creatinine concentration \>1.5 times the ULN at screening. Estimated glomerular filtration rate (GFR) \<60 mL/min/1.73 m2 is exclusionary.
• •* Bilirubin or alkaline phosphatase level \>2.5 × the ULN at screening.
• •* Glucose \<50 mg/dL or \>450 mg/dL despite adequate anti-hyperglycemic treatment.
• •* Platelet count \<100 × 109/L.
• •3. History of bacteremia or other serious bacterial or fungal infection requiring treatment with intravenous antibiotics within 84 days (12 weeks) prior to treatment with study therapy other than a treated urinary tract infection.
• •4. Known infection with human immunodeficiency virus (HIV).
• •5. Seropositive for hepatitis C or hepatitis B.
• •6. Known history of seizures.
• •7. Evidence of cerebral hemorrhage within the last 6 months or recent intracerebral hematomas detected by brain CT or MRI.
• •8. Hypertension with systolic blood pressure (SBP) \>185 mmHg or diastolic blood pressure (DBP) \>120 mmHG (mean of 3 consecutive arm cuff readings over 20 to 30 minutes).
• •9. High clinical suspicion of septic embolus.
• •10. History of major trauma at time of stroke.
• •11. History of malignancy within 5 years except basal cell or squamous cell carcinoma of the skin or remote history of cancer now considered cured or positive Pap smear with subsequent negative follow up.
• •12. Known allergy to non-steroidal anti-inflammatory drugs (NSAIDs).
• •13. Known allergy to both gadolinium and iodine based contrast agents for MRI preventing the ability to conduct either one of these procedures.
• •14. Patient has received an investigational agent within 90 days or 5 half-lives, whichever is longer, prior to treatment with study therapy or planned participation in another therapeutic trial prior to the completion of this study.
• •15. Patients with very light neurological symptoms (NIHSS score of \<3) or with rapidly improving symptoms before the start of treatment.
• •16. Patients with serious neurological disorders (NIHSS score ≥22) or serious consciousness disorders before the start of treatment.
• •17. Patients with functional disorders (mRS score \>2) before onset of the stroke.
• •18. Patients who have been administered drugs that are not allowed to be administered concomitantly with any anti-thrombotic agents after onset of the stroke.
• •19. Patients who are forbidden to undergo DTI-MRI.
• •20. Patients with symptoms suggesting subarachnoid hemorrhage (SAH).
• •21. Patients with hemorrhage (gastrointestinal hemorrhage, urinary hemorrhage, retroperitoneal hemorrhage, or hemoptysis).
• •22. Patients who have been administered oral anticoagulants with values of the international normalized ratio (INR) of prothrombin time (PT-INR) \>1.7.
• •23. Patients who have a history of intracranial hemorrhage, or who have a disease considered to increase the risk of intracranial hemorrhage such as an intracranial tumor, cerebral aneurysm, or intracranial arteriovenous malformation, etc.
• •24. Patients who were operated on or injured their head or spinal cord within 3 months before onset of the stroke.
• •25. Patients who have a history of gastrointestinal or urinary tract hemorrhage within 21 days before onset of the stroke.
• •26. Patients who had a major surgery or serious trauma (except for head or spinal cord trauma) within 14 days before onset of the stroke.
• •27. Patients who had an organ biopsy, arterial puncture, or lumbar puncture within 14 days before the onset of the stroke.
• •28. Patients with severe hepatic dysfunction or severe renal dysfunction.
• •29. Patients with acute pancreatitis.
• •30. Patients with concurrent infectious endocarditis, moyamoya disease (Willis circle occlusion syndrome), aortic dissection, or neck trauma, etc.
• •31. Patients judged to be difficult in monitoring for 4 to 7 months by their physician.