Clinical trial NCT00821821: Safety and Pharmacokinetics of MCI-186 in Subjects With Acute Ischemic Stroke
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Ischemic Stroke (AIS)
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2009-01-14
Enrollment: 36
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Number of Participants That Experienced Adverse Events
timeFrame: 87days
Secondary outcomes:
measure: Plasma MCI-186 Pharmacokinetics
timeFrame: 72 hours
measure: mRS, NIHSS, Barthel Index
timeFrame: throughout study
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Newcastle
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS Foundation Trust
Study officials:
affiliation: Information at Mitsubishi Pharma Europe
name: Professor
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1159/000353680. Epub 2013 Oct 12.