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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier:
NCT00821821
First received: January 13, 2009
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Acute Ischemic Stroke (AIS)
Drug: MCI-186
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by Mitsubishi Tanabe Pharma Corporation:

Primary Outcome Measures:
  • Number of Participants That Experienced Adverse Events [ Time Frame: 87days ] [ Designated as safety issue: Yes ]
    Additional Outcome Measures are included in Tables for Serious Adverse Events and Other Adverse Events to report their numbers and frequency.


Secondary Outcome Measures:
  • Plasma MCI-186 Pharmacokinetics [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    The geometric mean values of MCI-186 plasma concentration at the end of the infusion (at 72h) in cohorts 1 and 2 were determined.

  • mRS, NIHSS, Barthel Index [ Time Frame: throughout study ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: February 2009
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MCI-186 Drug: MCI-186

Cohort 1: Edaravone: circa 1000 mg / 72-hour infusion

Cohort 2: Edaravone: circa 2000 mg / 72-hour infusion

Other Name: Edaravone
Placebo Comparator: Placebo Group Drug: Placebo

Cohort1:circa 1000mg / 72-hour infusion matching placebo

Cohort2:circa 2000mg / 72-hour infusion matching placebo


  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00821821

Locations
Finland
Helsinki University Central Hospital
Helsinki, Finland
Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
United Kingdom
Newcastle upon Tyne Hospitals NHS Foundation Trust
Newcastle, United Kingdom
Sponsors and Collaborators
Mitsubishi Tanabe Pharma Corporation
Investigators
Study Chair: Professor Information at Mitsubishi Pharma Europe
  More Information

Publications:
Responsible Party: Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier: NCT00821821     History of Changes
Other Study ID Numbers: MCI-186-E04
Study First Received: January 13, 2009
Results First Received: January 5, 2014
Last Updated: April 7, 2014
Health Authority: Finland: Finnish Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Cerebral Infarction
Ischemia
Stroke
Brain Diseases
Brain Infarction
Brain Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Pathologic Processes
Vascular Diseases
Phenylmethylpyrazolone
Antioxidants
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on October 29, 2014