E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse Events (safety and tolerability) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |