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 | 7 |
E.1.2 | Level | VTc |
E.1.2 | Classification code | 10012271 |
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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 evaluate the efficacy of donepezil on cognition (MMSE) in patients who are currently being treated with memantine, and are switched to donepezil because treatment with memantine is lacking efficacy or is not well tolerated |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effects of donepezil on other clinically relevant measures including behaviour (NPI), physician and caregiver satisfaction/ease of use, global function (CGI-I), social behaviour (Caregiver Diary), safety and tolerability in this patient group. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients aged 50 years or over, both men and women. Women of childbearing potential or <2 year post-menopausal must be practising an approved method of contraception and have negative serum b-HCG at screening (women who are breastfeeding are excluded). Written informed consent to participation. Patients with moderate to severe Alzheimer’s disease with an MMSE score between 5-17 (inclusive). Diagnostic evidence of probable or possible Alzheimer’s disease consistent with DSM-IV and NINCDS-ADRDA criteria made by the site physician at the time of the screening visit. This evidence must be fully documented in the patient’s file prior to the baseline visit. CT or MRI within the last 18 months consistent with a diagnosis of Alzheimer’s disease without any other clinically significant co-morbid pathologies found. If there has been a significant change in clinical status suggestive of stroke or other possible neurological disease with onset between the time of the last CT or MRI and the screening evaluation, the scan should be repeated if considered appropriate by the investigator. The patient must be capable of completing all procedures scheduled during the screening and baseline visits including all efficacy parameters (i.e. psychometric tests). Patients must have a reliable caregiver or family member who agrees to accompany the patient to all clinic visits, provide information about the patient as required by the protocol, and ensure compliance with the medication schedule. The patient must be currently taking memantine at the recommended dose (10 mg bid) for at least 3 months prior to the screening visit and maintained until the baseline visit. Treatment of the patient with memantine is judged by the clinician at the time of screening as lacking efficacy or not well tolerated. Clinical laboratory values within normal limits, and within the sponsor’s guidelines, or, if abnormal, considered and documented as not clinically significant by the investigator. Health: otherwise healthy and ambulatory or ambulatory-aided (i.e., walker, cane or wheelchair). Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for compliance with testing procedures. Patients with stable insulin-dependent diabetes or diabetes stabilized by diet and/or oral hypoglycaemic agents are eligible provided they are monitored regularly to ensure adequacy of control. Patients with known diabetes should have an HbA1C of < 10% at screening. Patients with controlled hypertension (sitting diastolic BP < 95 mmHg), right bundle branch block (complete or partial), and pacemakers may be included in the study. Patients with thyroid disease may also be included in the study provided they are euthyroid and stable on treatment for at least 3 months prior to screening. Stable treatment must be maintained throughout the study. Patients with vitamin B12 deficiency who are on a stable dose of medication for at least 3 months prior to screening, and who have normal serum B12 levels at screening, will be eligible. This stable dose must be maintained throughout the study. |
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E.4 | Principal exclusion criteria |
Patients with a known hypersensitivity to donepezil, piperidine derivatives, or any of the excipients used in the formulation of donepezil Patients with active or clinically significant conditions affecting absorption, distribution or metabolism of the study medication. Patients who have been treated with a cholinesterase inhibitor in the 3 months prior to screening visit. Patients treated with any investigational drug within 30 days of screening visit. Patients without a reliable caregiver, or patients or caregivers who are unwilling or unable to complete any of the outcome measures and fulfill the requirements of this study. Nursing home patients will be excluded from entering the study. Likewise, patients for whom institutionalization is being considered within the next 3 months should also be excluded. Patients with clinically significant obstructive pulmonary disease or asthma. Patients with a recent (< 2 years) haematologic/oncologic disorders. Evidence of active clinically significant and unstable gastrointestinal, endocrine or cardiovascular system disease. Evidence of severe hepatic or renal impairment. Patients with a current DSM-lV diagnosis of Major Depressive Disorder (MDD), or any current primary psychiatric diagnosis other than Alzheimer’s disease (as per DSM-lV). Patients who, in the judgment of the investigator, represent a suicide risk. Patients with dementia complicated by other organic disease or Alzheimer’s disease with delirium (DSM 290.30 or 290.11) are excluded. Depression or delusions are common in Alzheimer’s disease, but patients with pronounced severe symptoms such that they warrant an alternative concurrent diagnosis, should be excluded. Patients with a known or suspected history of alcoholism or drug abuse (within the past 10 years). Any condition which would make the patient or the caregiver, in the opinion of the investigator or sponsor, unsuitable for the study. Patients who have taken or are taking any unapproved prior or concomitant medication as defined in the protocol. Patients with a history of seizures or seizure disorders. Patients must be able to swallow tablet medication. No crushing of tablets is allowed. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mini Mental State Examination (MMSE): The MMSE is a brief test to assess the cognitive status of the patient. The 30-point test includes items that evaluate orientation to time and place, immediate and delayed recall, attention and language. The MMSE will be administered by the same trained rater at each visit. |
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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 | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
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.8.5 | 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 | 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 | 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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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 | 0 |
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 | 0 |