E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute stroke (ischemic and hemorrhagic strokes, starting within 4 days of onset) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048863 |
E.1.2 | Term | Hemorrhagic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055221 |
E.1.2 | Term | Ischemic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
1. Can a 12-week course of donepezil improve motor recovery in acute stroke ?
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E.2.2 | Secondary objectives of the trial |
1. Can variability in outcome be predicted by both initial deficit and change in deficit over the first few days (i.e. for the duration of their stay in a Hyperacute Stroke Unit; usually 2-4 days)? 2. Is response to donepezil in acute stroke patients related to lesion size, location and/or functional brain MRI parameters at baseline? 3. Is variability in outcome related to functional MRI characteristics at baseline? 4. Does donepezil alter changes in functional connectivity over 12 weeks relative to placebo?
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients diagnosed with acute stroke diagnosed on clinical and neuroimaging grounds who can enter the trial within the 1st week of stroke onset, and who have new motor dysfunction of an upper limb. Motor impairment should be moderate - severe (<50/66 in UE-FM score). 2. Age: above 18 years old. 3. Patients able and willing to partake in motor tests, and to return for follow-up visit at 12 weeks. 4. Able to understand English. |
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E.4 | Principal exclusion criteria |
1. Contraindications for donepezil: pregnancy (Female patients of child-bearing potential will be asked if there is any possibility that they might be pregnant. If there is any uncertainty, or a likelihood that they are pregnant, this will qualify as an exclusion criterion); moderate – severe asthma (i.e. regular treatment prescribed for this); bradycardia, syncope, 2nd or 3rd degree heart block, acute or decompensated heart failure; peptic ulcer diagnosed endoscopically and on treatment for this; epilepsy; Parkinson’s disease; end-stage renal failure or creatinine > 300 mcmol/l; genito-urinary tract or gastrointestinal tract obstruction; gastrointestinal tract hemorrhage; myasthenia gravis; on anti-cholinergic therapy for bowel or bladder overactivity 2. Other: functionally-significant cognitive impairment (i.e. dementia); significant receptive aphasia (i.e. such that cannot understand purpose or details of trial, and will be unable to cooperate with task instructions); significant physical infirmity as judged by treating physician (e.g. severe organ failure; terminal cancer). 3. Contraindications for MRI (this only pertains for the subset of patients entering the MRI substudy, or subjects without prior MRI, but is not a contra-indication to the main study providing a diagnosis of stroke is clear from CT): claustrophobia, metal implants including pacemaker. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Motor Scores - Fugl-Meyer Upper Extremity Motor Score (out of 66);
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Laptop-based task: motor accuracy (%) 2. National Institute for Health Stroke Scale (NIHSS) 3. modified Rankin Score (mRS); side-effects (self-reported; questionnaire) 4. Functional MRI measures of blood-oxygenation level dependent (BOLD) activation strength and resting-state netowork connectivity |
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E.5.2.1 | Timepoint(s) of evaluation of this 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 | No |
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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |