Safety Study of a Recombinant Human Plasminogen Activator to Treat Acute Ischemic Stroke.


Phase 1/2 Results

Eligibility Criteria

Inclusion Criteria

- Subjects with cerebral ischemia at any location producing a serious measurable deficit by NIHSS scale and who received study medication within 5 hours after the onset of the symptom. A serious measurable deficit by NIHSS was defined as the NIHSS  9 and  20 (for brain stem stroke, patients with NIHSS > 20 were included).
- Subjects were  18 years old, of either sex.
- Subjects or his/her legal guardians demonstrated their willingness to participate in the study and comply with its procedures by signing a written informed consent.
- Subjects with Modified Rankin Scale > 1.

Exclusion Criteria

- Onset of symptoms on awaking from sleep.
- Intracranial bleeding detected on a pretreatment head computerized tomographic (CT) scan.
- Clinical presentation suggested a subarachnoid hemorrhage even if the head CT scan was normal.
- Head CT showed the evidence of early infarct sign > 1/3 of MCA territory.
- Subjects had generalized seizure at the onset of the stroke.
- Subjects with blood glucose < 50 mg/dl or > 400 mg/dl.
- Subjects had another stroke, head trauma, cerebral hemorrhage or ischemic infarction within 3 months prior to the study entry.
- Subjects with a significant surgery within 14 days prior to study entry.
- Subjects with a history of gastrointestinal or urinary tract hemorrhage within 21 days prior to the study entry.
- Subjects with lumbar puncture or arterial puncture of non-compressible site within 14 days prior to the study entry.
- Subjects had known bleeding diathesis.
- Subjects with other serious medical illness that interfered with the study.
- Subjects had a platelet count < 100,000/mm3; hematocrit < 30%.
- Subjects with other serious medical illness that interfered with the study.
- Subjects had aPTT or PT > upper normal limit.
- Subjects had uncontrolled hypertension (> 180 mmHg systolic or > 110 mmHg diastolic) without additional anti-hypertensive medication at screening visit.
- Subjects with recent transmural myocardial infarction and evidence of pericarditis within 3 weeks prior to the enrollment.
- Subjects had intracranial neoplasm, arteriovenous malformation, or aneurysm.
- Subjects had hemostasis defects including secondary to severe hepatic or renal disease.
- Subjects with history of drug or alcohol abuse within 1 year prior to the study entry.
- Subjects had significant hepatic dysfunction (SGOT/SGPT  3 x upper normal limit).
- Subjects had serum creatinine level  2 x upper normal limit or on renal dialysis.
- Subjects had administration of any other investigational drug within 30 days prior to study entry.
- Woman who was pregnant or nursing.
- Subjects had used other thrombolytics (streptokinase, tissue plasminogen activator, urokinase, anisoylated plasminogen streptokinase activator complex, anticoagulants).
- Subjects had severe cardiac disease (New York Heart Association Functional Classification III and IV).
- Subjects had history of cancer except inactive non-melanoma skin cancer, in situ carcinoma of the cervix, or any cancer in patient’s disease free for more than 5 years.
- Subjects had any clinically significant deviation from normal in the physical examination that, in the investigator judgment, interfered with the study evaluation or affect subject safety.
- Subjects with history of lupus.
- Vasculitis was the cause of ischemic stroke.
- Subjects had been enrolled in this study previously.