E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Middle cerebral artery ischemic stroke |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
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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 compare the efficacy MK-0724 8 mg/kg/hr x 1 hr daily for 7 days to placebo in patients with middle cerebral artery ischemic stroke using the Day 90 Action Research Arm Test (ARAT) scores. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy MK-0724 8 mg/kg/hr x 1 hr daily for 7 days to placebo in patients with middle cerebral artery ischemic stroke using (1) the Day 90 Stroke Arm Strength score, (2) the Day 90 modified Rankin Scale (mRS), and (3) the Day 90 Barthel Index (BI) score. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 18-80, inclusive, not pregnant Must be randomized into the study and begin receiving the first infusion of blinded study medication between 8 hours to 36 hours after the initial onset of stroke symptoms Stroke is ischemic in origin, middle cerebral artery territory No significant neglect (score <2 on NIHSS question # 11) baseline NIHSS of 6-18 inclusive baseline aged adjusted NIHSS (NIHSS + age/5) score of 19-32 Contralateral arm weakness (a score ≥ 1 NIHSS question # 5) Persistent neurological deficit >60 min.
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E.4 | Principal exclusion criteria |
Stroke in 3 months preceding index stroke Baseline imaging ASPECTS ≤ 3 Treatment with thrombolytic therapies: tPA, urokinase, streptokinase, intra-arterial t-PA or devices for reperfusion, thromboectomy Evidence of a non-ischemic mechanism, subarachnoid hemorrhage, or intracerebral and/or intraventricular hemorrhage, clinically significant cerebral edema Reduced level of consciousness (≥ 2 on NIHSS question 1a) Dense hemiplegia (NIHSS question 5 = 4 and question 6 = 4) Pre-stroke Modified Rankin score of ≥2 Rapidly improving neurological signs and symptoms Premorbid history suggestive of cognitive impairment, dementia, aphasia, unable to carry out ADL independently Previous disorder that would confound interpretation of the neurological scales Severe coexisting or terminal systemic disease (including HIV/AIDS) or explicit comfort care status History of Malignancy ≤ 5 years Body weight of >125 kg Pregnancy or lactation Serum creatinine > 2mg/dL. ALTor AST ≥ 150% of the ULN with concomitant bilirubin > 2 mg/dL and/or ascites Decompensate CHF ECG: QTc>480 ms or ventricular arrhythmias or a Mobitz Type 1 or greater AV block Participation in previous Ono-2506 study or other investigational study within 30 days
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is the Day 90 Action Research Arm Test (ARAT) score for patients treated with MK-0724 8 mg/kg/hr x 1 hr daily for seven days as compared to those treated with placebo.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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See protocol section 3.5.4 Interim Analyses |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |