E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of acute stroke. |
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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 |
The primary objective of the study is to determine the efficacy of a 72 hour infusion of SUN N4057 in subjects with clinical findings of an acute ischemic stroke and an MRI demonstrating a measurable penumbra (perfusion-weighted imaging [PWI] minus diffusion-weighted imaging [DWI] volume). Efficacy will be determined by comparing the proportion of subjects with no growth in stroke lesion volume between Screening and Day 28, with stroke lesion volume assessed by DWI at Screening and by FLAIR (fluid-attenuated inversion recovery) at Day 28, in the SUN N4057 group versus the placebo group. |
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E.2.2 | Secondary objectives of the trial |
The study drug was administered for a period of 72 hours, and patients were followed up for 90 days.
1. To compare the SUN N4057 group versus the placebo group for: - The absolute change in stroke lesion volume and percent change in stroke lesion volume between Screening to Day 28; - The clinical outcomes at Day 28 and 90 using the individual clinical scales (Modified Rankin Scale, Barthel Index, and National Institutes of Health Stroke Scale [NIHSS]); - The global test statistic (GTS) at Days 28 and 90 using the results on the Modified Rankin Scale, Barthel Index, and NIHSS; - All-cause-mortality at Day 28 and 90; and 2. To assess the safety and tolerability of SUN N4057 in subjects with acute stroke.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
General Inclusion Criteria 1. Males or females >= 18 and <= 85 years of age at randomization. Female subjects must be either: - Surgically sterile - Post-menopausal for at least 1 year - Non pregnant confirmed by serum pregnancy test, and using a method of birth control that is acceptable to the investigator. 2. Neurological examination demonstrating localizing cortical signs 3. Receipt of study drug less than 6 hours (50% of subjects) or between 6 and 9 hours, inclusive, (50% of subjects) after the onset of symptoms (for un-witnessed stroke, last time seen in normal state or at bedtime for un-witnessed stroke during sleep) 4. Signed informed consent from subject or a legally acceptable representative 5. NIHSS score of 6 - 22, inclusive, or at least 2 on the aphasia item of the NIHSS with a location of MRI findings consistent with aphasia
MRI-Determined Inclusion Criteria 1. Acute ischemic stroke with substantial cortical involvement in the middle cerebral artery (MCA) distribution, as verified by the Screening DWI abnormality and/or Screening PWI abnormality. (Note: white matter involvement, in addition to cortex, is not an exclusion.) 2. DWI with the longest diameter in any plane of at least 2 cm and no longer than 8 cm 3. PWI with the longest diameter in any plane of at least 3 cm 4. Screening PWI abnormality exceeding the Screening DWI abnormality (mismatch) by 50% in volume or > 1 cm in diameter
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E.4 | Principal exclusion criteria |
General Exclusion Criteria: 1. Two or more of the following: a. Reduced level of consciousness (score 2 on NIHSS Q1a) b. Forced eye deviation or total gaze paresis (score of 2 on NIHSS Q2) c. Dense hemiplegia (no movement) of upper and lower extremities (score of 4 on NIHSS Q5 regarding motor arm and a score of 4 on NIHSS Q6 regarding motor leg) 2. Pre-stroke Modified Rankin score 2 at Screening 3. Rapid neurological improvement from Screening up to the start of drug infusion 4. Persistent systolic blood pressure (SBP) > 220 mmHg and/or diastolic blood pressure (DSP) > 120 mmHg (confirmed by at least three readings taken at least 3 minutes apart) prior to randomization. If subsequent readings are consistently below these levels, either spontaneously or following mild antihypertensive therapy, the subject may be enrolled. 5. Aggressive anti-hypertensive therapy required to maintain blood pressure at acceptable levels 6. Female subjects who are pregnant and/or nursing, confirmed by serum pregnancy test 7. Administration of an investigational product within the past 30 days 8. Currently taking any selective serotonin reuptake inhibitor (SSRI) and/or other medications listed in Section 9.9 and Attachment II of the protocol 9. Significant renal dysfunction as defined by a serum creatinine > 2.5 mg/dL and a creatinine clearance < 30 mL/min based on Cockroft-Gault formula 10. Significant hepatic disease as defined by liver function tests (LFT) 3 times the upper limit of normal 11. Seizure during the current stroke episode 12. Received, or is a candidate to receive, thrombolytics for the current stroke episode 13. Life expectancy of less than 90 days 14. Another significant neurologic disease or previous stroke in addition to the current stroke that would, in the opinion of the Investigator, interfere with the neurological assessment 15. Myocardial infarction within 3 months of study entry 16. Unstable angina pectoris 17. Congestive heart failure with symptoms either at rest or minimal exertion (New York Heart Association [NYHA] Class III or IV) 18. Cardiac conduction system abnormality including second or third degree atrioventricular (AV) block 19. Sinus bradycardia (resting heart rate< 50 beats per minute) or a history of sick sinus syndrome 20. Evidence of QTc prolongation (>450 milliseconds) on Screening ECG 21. Known history of symptomatic orthostatic hypotension 22. Persistent elevation of glucose > 300 mg/dL during screening 23. Cancer under active treatment 24. Received known cytochrome P450 3A4 inhibitors including azole antifungal agents (e.g., ketoconazole, itraconazole) within 24 hours prior to Hour 0 and for 3 days after Hour 72. An appropriate longer washout period is required for drugs with a longer half-life.
MRI-Determined Exclusion Criteria 1. Intracranial hemorrhage as verified by the Screening MRI (or a computerized tomography [CT] scan performed pre-screening) 2. Subacute stroke in a symptomatic region of the brain verified by significant T2 shine through on the Screening FLAIR MRI 3. Significant mass effect, edema, or midline shift including Screening DWI abnormality greater than 2/3 of the MCA territory 4. DWI longest diameter greater than 8 cm or less than 2 cm 5. No Screening PWI abnormality and therefore no PWI/DWI mismatch 6. Contraindication to MRI (ferrous implants, cardiac pacemakers, claustrophobia, or known sensitivity to MRI contrast agents) 7. Severe agitation that precludes MRI
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E.5 End points |
E.5.1 | Primary end point(s) |
Although the treatment period will last 72 hours, patients will be followed up for 90 Days. MRIs will be performed at Screening, Hour 12 of administration, and Day 28 of the study. Efficacy will be assessed by comparing the proportion of subjects who have no growth in stroke lesion volume as assessed by DWI on MRI at Screening to stroke lesion volume assessed by FLAIR on Day 28 (primary end-point). |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Also sequential-group. Dose-escalation. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
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 | Information not present in EudraCT |
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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Date that all data clarifications have been completed. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |