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

Acute Ischemic Stroke (AIS) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00821821
• Other study ID #: MCI-186-E04
• Status: Completed
• Phase: Phase 2
• First received: January 13, 2009
• Last updated: April 7, 2014
• Start date: February 2009
• Est. completion date: November 2010

Study information

• Verified date: April 2014
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Finland: Finnish Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Acute Ischemic Stroke (AIS)
• Ischemia
• Stroke

Intervention

Drug:
• MCI-186
Cohort 1: Edaravone: circa 1000 mg / 72-hour infusion Cohort 2: Edaravone: circa 2000 mg / 72-hour infusion
• Placebo
Cohort1:circa 1000mg / 72-hour infusion matching placebo Cohort2:circa 2000mg / 72-hour infusion matching placebo

Locations

Country	Name	City	State
Finland	Helsinki University Central Hospital	Helsinki
Netherlands	Erasmus Medical Center	Rotterdam
United Kingdom	Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation

Countries where clinical trial is conducted

Finland,  Netherlands,  United Kingdom, 

References & Publications (1)

Kaste M, Murayama S, Ford GA, Dippel DW, Walters MR, Tatlisumak T; MCI-186 study group. Safety, tolerability and pharmacokinetics of MCI-186 in patients with acute ischemic stroke: new formulation and dosing regimen. Cerebrovasc Dis. 2013;36(3):196-204. d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	mRS, NIHSS, Barthel Index		throughout study	No