E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
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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 |
The primary objective is to determine the safety, tolerability, and efficacy of 3 doses of Lecozotan (SRA-333) SR (2 mg, 5 mg and 10 mg) in patients with mild to moderate Alzheimer's Disease (AD). |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to estimate comparative safety, tolerability and efficacy versus donepezil over a 12-week period in patients with AD and to measure the responsiveness of patient and caregiver-reported outcomes instruments. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosis of probable AD according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria. 2. Men and postmenopausal or surgically sterile women aged 50 years or older. Postmenopausal women must have had at least 12 months of spontaneous amenorrhea. Surgically sterile women are defined as those who have had a hysterectomy, bilateral ovariectomy (oophorectomy), or bilateral tubal ligation. 3. Mini-Mental State Examination (MMSE) score of 12 to 26. 4. Rosen Modified Hachinski Ischemic score =< 4. 5. Lives at home with appropriate caregiver, or community dwelling with caregiver capable of accompanying patient on all clinic visits and visiting the patient at least daily for the duration of the study. 6. Computed tomography (CT) or magnetic resonance imaging (MRI) scan within the past 2 years (performed after onset of dementia) consistent with the diagnosis of AD. There should be no clinical evidence of stroke since completion of the imaging study (one lacuna, in areas not related to cognitive function, eg, cerebellum or deep white matter, will not exclude the patient). 7. Able to give signed and dated written informed consent in accordance with local regulations. The patient’s caregiver will also consent to participate in the study. 8. Able to complete all required neuropsychological tests. 9. Fluency in local language. 10. Receiving stable doses of medications for the treatment of nonexcluded medical conditions for 30 days before screening. 11. Able to participate in all scheduled evaluations and complete all required tests. 12. In the opinion of the investigator, the patient and caregiver will be compliant and have a high probability of completing the study. |
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E.4 | Principal exclusion criteria |
1. Significant neurological disease other than AD that may affect cognition (eg, epilepsy, Parkinson disease) or ability to complete the study. 2. Current diagnosis of a major depressive disorder or other major psychiatric symptoms included in psychiatric disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM IV-TR), criteria. 3. Current clinically significant systemic illness that, in the judgment of the investigator, is likely to deteriorate or affect the patient’s safety, influence cognitive assessment, or ability to complete the study. 4. History of seizure, except febrile childhood febrile seizures. 5. History of clinically evident stroke or clinically significant carotid or vertebrobasilar stenosis or plaque. 6. Myocardial infarction within the last 3 months. 7. History of cancer within the last 5 years, with the exception of nonmetastatic basal and/or squamous cell carcinoma of the skin 8. Excessive smoking (greater than 20 cigarettes a day). 9. History of alcohol or drug dependence within the last 1 year. 10. Hamilton Psychiatric Rating Scale for Depression, 21 items (HAM-D21) score > 17. 11. Any clinically significant abnormality in physical examination, vital signs, electrocardiogram (ECG), or clinical laboratory test results that in the judgment of the investigator, is likely to deteriorate or affect the patient’s safety or ability to complete the study. 12. History of any clinically important multiple drug allergies, that will compromise the patient’s safety during the study. 13. Use of prescription or nonprescription medications for medications for cognitive enhancement, (including memantine, and the use of cholinesterase inhibitors) within 3 months of the baseline visit. History of clinically significant side effects attributable to cholinesterase inhibitors and any history of intolerance, or lack of response to cholinesterase inhibitors. 14. Any use of experimental drugs investigational drugs or procedures, including experimental medications for AD, within 30 days of baseline visit. 15. Current use of anticonvulsant, anti Parkinson, antipsychotic, antidepressant medication and buspirone within 30 days of baseline visit (except for fluoxetine, which is excluded within 60 days of baseline). 16. Regular use of narcotic medications within 30 days of baseline visit. 17. Treatment with strong inhibitors of the cytochrome P450 3A4 isoenzyme system (i.e. ketoconazole, itraconazole, erythromycin, clarithromycin) within 1 week of baseline visit.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints will be the change from baseline in the Alzheimer's Disease Assessment Scale-Cognitive Behavior (ADAS-Cog) total score and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) at week 12. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Health Outcomes Assessments |
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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) | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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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Last visit of the last subject: Patients who complete Week 12 evaluations and meet the eligibility criteria at baseline visit, will be offered continued treatment in a long-term extension study (Protocol 3098B1-202). |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |