Dose Finding Study of MCI-186 in Acute Ischemic Stroke

Study Overview
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Brief Summary
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To investigate the efficacy and safety of MCI-186 (bolus followed by continuous infusion) in acute ischemic stroke patients through a double-blind, parallel-group comparison with the existing MCI-186 dosing regimen (administration twice daily for 14 days) as the control.

Official Title
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Dose Finding Study of MCI-186 in Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Continuous infusion high-dose MCI-186
* Drug: Continuous infusion low-dose MCI-186
* Drug: Continuous infusion placebo
* Drug: Approved dosing regimen MCI-186
* Drug: Approved dosing regimen placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients from whom written consent to study participation has been obtained, either from the patient personally or from the patient's legal guardian Patients with age at consent between 20 and 85 years, inclusive Patients for whom study treatment can be initiated within 24 hours after onset Patients with confirmed new ischemic area only in the supratentorial region on MRI Patients with neurological signs equivalent to between 4 and 22, inclusive, on the NIHSS Exclusion Criteria: Patients with disability equivalent to an mRS score of 2 or more from before onset Patients being treated with antibiotics for an infection at registration Patients who have received or are planning to receive treatment for their primary disease with a prohibited concomitant medication (e.g., a thrombolytic drug) or with a prohibited concomitant therapy (e.g., intravascular therapy) Patients for whom the (sub)investigator judges the efficacy endpoints (e.g., NIHSS, mRS, BI) that have been selected for this study can not be measured appropriately, such as patients who are not expected to achieve improvement of 4 or more on the NIHSS because of nerve symptoms that have been present since before the onset of cerebral infarction, Alzheimer's dementia patients, or Parkinson's disease patients Patients with severe consciousness disturbances (Japan coma scale ≥ 100) Patients with clear concurrent peripheral vascular disease or peripheral neuropathy for whom the (sub)investigator judges the neurological tests could not be performed properly Patients with severe renal impairment (e.g., patients with eGFR < 30) Patients with severe hepatic impairment (e.g., ALT, AST, or gamma-GTP > 2.5 X ULN) Patients with platelet count < 100,000/mm3 Patients diagnosed by MRI on admission with a disease other than stroke (e.g., intracranial bleeding, subarachnoid bleeding, arteriovenous malformations, Moyamoya disease, brain tumor) or with cerebral aneurysm with a maximum diameter > 7 mm Patients with prior or current drug abuse or alcohol dependence Patients with prior (or current) malignant tumor within 5 years before stroke onset Patients with a past history of hypersensitivity to edaravone drug products Patients with concurrent heart disease severe enough to warrant admission and treatment (e.g., acute myocardial infarction, cardiac failure) and with problems with their overall condition judged by the (sub)investigator to be unsuitable for study participation Patients for whom MRI tests cannot be performed Male or female patients who do not consent to practice contraception from the date of consent until the day after the administration of the last dose of study drug Patients who are pregnant or nursing, or who could be pregnant Patients who have received other investigational drugs in the 12 weeks prior to consent acquisition Patients with body weight ≥ 100 kg Patients otherwise judged unsuitable for study participation by the (sub)investigator

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 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: Continuous infusion high-dose group (Group H)<br>High-dose MCI-186 will be administered as a bolus, and then as a continuous infusion. In addition, a placebo will be administered as an intravenous infusion twice a day over 30 minutes. | Drug: Continuous infusion high-dose MCI-186<br>* intravenous injection<br>Drug: Approved dosing regimen placebo<br>* intravenous injection<br>|
| Experimental: Continuous infusion low-dose group (Group L)<br>Low-dose MCI-186 will be administered as a bolus, and then as a continuous infusion. In addition, a placebo will be administered as an intravenous infusion twice a day over 30 minutes. | Drug: Continuous infusion low-dose MCI-186<br>* intravenous injection<br>Drug: Approved dosing regimen placebo<br>* intravenous injection<br>|
| Experimental: Approved dosing regimen group (control group)<br>A placebo will be administered as a bolus, and then as a continuous infusion. In addition, MCI-186 30 mg will be administered as an intravenous infusion twice a day over 30 minutes. | Drug: Continuous infusion placebo<br>* intravenous injection<br>Drug: Approved dosing regimen MCI-186<br>* intravenous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with National Institutes of Health Stroke Scale (NIHSS) score improved. | NIHSS is a scale to objectively quantify the neurologic impairment caused by a stroke. Possible scores range from 0 (no stroke symptoms) to 40(severe stroke). | Baseline up to Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of National Institutes of Health Stroke Scale (NIHSS) | NIHSS is a scale used to objectively quantify the neurologic impairment caused by a stroke. Possible scores range from 0 (no stroke symptoms) to 40 (severe stroke). | Day 14, at discharge(from Day15 to after 3 months) and after 3 months | 
| Comparison of modified Rankin Scale (mRS) | mRS is a scale for measuring the degree of disability caused by a stroke. Possible scores range from Grade 0 (no symptoms) to Grade 6 (death). | at discharge(from Day15 to after 3 months) and after 3 months | 
| Comparison of Barthel Index (BI) | BI is a scale for measuring performance in Activities of Daily Living (ADL). Possible scores range from 0 (worst) to 100 (best). | at discharge(from Day15 to after 3 months) and after 3 months | 
| Comparison of Functional Independence Measure (FIM) | FIM is a scale used to evaluate the functional status. Possible scores range from 18 (worst) to 126 (best). | at discharge(from Day15 to after 3 months) and after 3 months |