Safety and Pharmacokinetics of MCI-186 in Subjects With Acute Ischemic Stroke

Study Overview
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Brief Summary
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The objectives of this study are to assess the safety, tolerability and local tolerance, and to investigate the plasma levels and terminal elimination half life of MCI-186, and to review the routine clinical and neurological assessments data of MCI-186 in subjects with acute ischemic stroke.

Official Title
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A Phase IIa, Multi-centre, Randomised, Double-blind, Placebo Controlled, Clinical Study Investigating the Safety, Tolerability and Pharmacokinetics of MCI-186 in Subjects With Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke (AIS)

Intervention / Treatment
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* Drug: MCI-186
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Full functional independence prior to the present stroke (as evidenced by a pre-morbid modified Rankin Scale score of 0-2 Clinical diagnosis of acute stroke with CT scan ruling out intracranial hemorrhage Onset of symptoms within 1-24 hours of commencement of infusion of study drug Measurable deficit on NIHSS (as evidenced by a score of 3-15) Full consciousness (i.e. the score for NIHSS item 1a=0) Written valid informed consent is obtained from the subject or his/her next of kin or legal representative if the subject is fully conscious (i.e. the score for NIHSS item 1a = 0) but unable to read and/or sign the ICF, in accordance with National legislation and local IRB requirements Exclusion Criteria: Subjects who are unlikely to complete the infusion of investigational product and/or are unlikely to undergo active medical management during that period due to a severe clinical condition Subjects with severe illness with life expectancy less than 6 months Body weight in excess of 120 kg Subjects who have received rTPA or other thrombolytics (e.g. urokinase, streptokinase, reteplase, tenecteplase) within the previous 24 hours Likelihood of forbidden concomitant therapy such as vascular surgery, coronary artery bypass graft (CABG), valve replacement, or carotid endarterectomy (CEA) Evidence of cerebral herniation Subjects with confounding neurological diseases such as dementia Subjects with CADASIL, Moya Moya, or carotid dissection Subjects who have experienced a stroke within the previous 3 months (Note: subjects who have recently experienced a TIA, but whose premorbid mRS prior to their stroke is 0-2, will be allowed to enter the study) Evidence from admission imaging tests of infarction involving >1/3 of MCA territory, or entire ACA territory involvement, or internal carotid artery (ICA) occlusions without coexisting separate occlusion of the middle cerebral artery (because of the difficulty distinguishing between chronic and acute ICA lesions in such subjects) Pathology other than cerebral infarction on any admission imaging tests (e.g. ICH or SAH, AV malformation, cerebral aneurysm, or cerebral neoplasm) Current or previous known excessive alcohol use or dependence Current known illicit drug use or dependence Participation in a previous clinical study within 30 days Subjects unlikely to be able and willing to attend all study follow-up visits Any other conditions which in the opinion of the investigator deem the subject ineligible for inclusion Females who are pregnant or intend to become pregnant or subjects (male and female) who do not agree to use effective contraception for 3 months after end of treatment

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MCI-186<br> | Drug: MCI-186<br>* Cohort 1: Edaravone: circa 1000 mg / 72-hour infusion Cohort 2: Edaravone: circa 2000 mg / 72-hour infusion<br>* Other names: Edaravone;|
| Placebo Comparator: Placebo Group<br> | Drug: Placebo<br>* Cohort1:circa 1000mg / 72-hour infusion matching placebo Cohort2:circa 2000mg / 72-hour infusion matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Experienced Adverse Events | Additional Outcome Measures are included in Tables for Serious Adverse Events and Other Adverse Events to report their numbers and frequency. | 87days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma MCI-186 Pharmacokinetics | The geometric mean values of MCI-186 plasma concentration at the end of the infusion (at 72h) in cohorts 1 and 2 were determined. | 72 hours | 
| mRS, NIHSS, Barthel Index |  | throughout study |