Dose Finding Study of MCI-186 in Acute Ischemic Stroke

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.

Study Overview

• Status: Terminated
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Continuous infusion high-dose MCI-186; Drug: Approved dosing regimen placebo; Drug: Continuous infusion low-dose MCI-186; Drug: Continuous infusion placebo; Drug: Approved dosing regimen MCI-186

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Investigational site 13
  • Aomori, Japan
    • Investigational site 39
  • Chiba, Japan
    • Investigational site 19
  • Chiba, Japan
    • Investigational site 28
  • Ehime, Japan
    • Investigational site 33
  • Fukui, Japan
    • Investigational site 10
  • Fukuoka, Japan
    • Investigational site 05
  • Fukuoka, Japan
    • Investigational site 09
  • Fukuoka, Japan
    • Investigational site 11
  • Fukuoka, Japan
    • Investigational site 12
  • Fukuoka, Japan
    • Investigational site 18
  • Fukuoka, Japan
    • Investigational site 21
  • Fukuoka, Japan
    • Investigational site 32
  • Fukuoka, Japan
    • Investigational site 37
  • Fukushima, Japan
    • Investigational site 07
  • Fukushima, Japan
    • Investigational site 08
  • Gifu, Japan
    • Investigational site 15
  • Gifu, Japan
    • Investigational site 23
  • Gunma, Japan
    • Investigational site 02
  • Hokkaido, Japan
    • Investigational Site 01
  • Hokkaido, Japan
    • Investigational site 22
  • Hyogo, Japan
    • Investigational site 06
  • Hyogo, Japan
    • Investigational site 30
  • Hyogo, Japan
    • Investigational site 42
  • Ishikawa, Japan
    • Investigational site 43
  • Iwate, Japan
    • Investigational site 27
  • Kanagawa, Japan
    • Investigational site 40
  • Kochi, Japan
    • Investigational site 24
  • Miyagi, Japan
    • Investigational site 35
  • Nagano, Japan
    • Investigational Site 16
  • Nagano, Japan
    • Investigational site 20
  • Okayama, Japan
    • Investigational site 44
  • Okinawa, Japan
    • Investigational site 41
  • Osaka, Japan
    • Investigational site 03
  • Osaka, Japan
    • Investigational site 25
  • Saga, Japan
    • Investigational site 38
  • Saitama, Japan
    • Investigational site 31
  • Shimane, Japan
    • Investigational site 14
  • Tochigi, Japan
    • Investigational site 29
  • Tochigi, Japan
    • Investigational site 36
  • Tokyo, Japan
    • Investigational site 17
  • Tokyo, Japan
    • Investigational site 45
  • Yamagata, Japan
    • Investigational site 34
  • Yamaguchi, Japan
    • Investigational site 04
  • Yamaguchi, Japan
    • Investigational site 26

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous infusion high-dose group (Group H); 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; intravenous injection; Drug: Approved dosing regimen placebo; intravenous injection
Experimental: Continuous infusion low-dose group (Group L); 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: Approved dosing regimen placebo; intravenous injection; Drug: Continuous infusion low-dose MCI-186; intravenous injection
Experimental: Approved dosing regimen group (control group); 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; intravenous injection; Drug: Approved dosing regimen MCI-186; intravenous injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mitsubishi Tanabe Pharma Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Actual): May 14, 2018
• Study Completion (Actual): May 14, 2018

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: November 14, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): September 24, 2018
• Last Update Submitted That Met QC Criteria: September 20, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Antioxidants; Free Radical Scavengers; Edaravone
• Other Study ID Numbers: MCI-186-J20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No