A Phase IIa, multi-centre, randomised, double-blind, placebo controlled, clinical study investigating the safety, tolerability and pharmacokinetics of two different infusion doses over 72 hours of a new regimen and new formulation of MCI-186 in subjects with acute ischemic stroke

• Conditions: Acute ischemic stroke

• Registration Number: EUCTR2008-003397-17-NL
• Lead Sponsor: Mitsubishi Tanabe Pharma Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-10-02
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Male or female, aged 40-80 years old
2. Full functional independence prior to the present stroke (as evidenced by a pre-morbid modified Rankin Scale score of 0-2)
3. Clinical diagnosis of acute stroke with CT scan ruling out intracranial hemorrhage
4. Onset of symptoms within 1-24 hours of commencement of infusion of study drug
5. Measurable deficit on NIHSS (as evidenced by a score of 4-15)
6. Full consciousness (i.e. the score for NIHSS item 1a=0)
7. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. 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.
2. Subjects unlikely to survive the acute period of stroke.
3. Subjects with severe illness with life expectancy less than 6 months.
4. Body weight in excess of 120 kg.
5. Subjects who have received rTPA or other thrombolytics (e.g. urokinase, streptokinase, reteplase, tenecteplase) within the previous 24 hours.
6. Subjects who have infection under antibiotic treatment at the enrollment.
7. Likelihood of forbidden concomitant therapy such as vascular surgery, coronary artery bypass graft (CABG), valve replacement, or carotid endarterectomy (CEA).
8. Evidence of cerebral herniation.
9. Subjects with confounding neurological diseases such as dementia.
10. Subjects with CADASIL, Moya Moya, or carotid dissection.
11. 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).
12. History of peripheral vascular disease.
13. Subjects with Diabetes Mellitus who have a history of peripheral neuropathy or significant evidence of peripheral neuropathy on routine neurological examination.
14. Known severe kidney disorder (or estimated creatinine clearance of <30 mL/min).
15. Known severe hepatic disorder, or elevated liver enzymes (at least 2 of ALT, AST, and gamma GT) greater than 3 times the upper limit of normal (=3 x ULN).
16. 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).
17. Pathology other than cerebral infarction on any admission imaging tests (e.g. ICH or SAH, AV malformation, cerebral aneurysm, or cerebral neoplasm)
18. Current or previous known excessive alcohol use or dependence.
19. Current known illicit drug use or dependence.
20. Participation in a previous clinical study within 30 days.
21. Subjects unlikely to be able and willing to attend all study follow-up visits.
22. Any other conditions which in the opinion of the investigator deem the subject ineligible for inclusion.
23. 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

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety, tolerability and local tolerance of two different intravenous infusion doses over 72 hours of a new dosing regimen and a new formulation of MCI-186 in subjects with acute ischemic stroke;Secondary Objective: 1) To investigate the steady state plasma levels and terminal elimination half life of two different intravenous infusion doses over 72 hours of a new dose regimen and a new formulation of MCI-186 in subjects with acute ischemic stroke<br><br><br>2) To review the routine clinical and neurological assessments data of AIS over a period of 87 days from the start of the intravenous infusion.<br>;Primary end point(s): Adverse Events (safety and tolerability)