| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| SEVERE ALZHEIMER’S DISEASE |
|
| 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 | 10001896 |
| E.1.2 | Term | Alzheimer's disease |
|
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
To explorecorrelations between inflammatory cytokines, behavioural symptoms and Aricept treatment response
To explore correlations between quality of life, behavioural symptoms and Aricept treatment response |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1 Age range: Patients ≥ 50 years.
2 Sex distribution: both men and women. Women must be two (2)-years post-menopausal or surgically sterile.
3 MMSE scores between 1 and 12 (inclusive).
4 Clinically significant behavioral pathology as measured by the Cornell Scale for Depression in Dementia(CSDD), defined as a total score on the CSDD of 5 or greater with at least one item rated 2 (severe) within the domains of Mood-Related Signs(Anxiety, Sadness, Lack of Reactivity, Irritability) or Behavioral Disturbances(Agitation, Retardation, Multiple Physical Complaints, Loss of Interest).
5 Diagnostic evidence of probable or possible Alzheimer’s disease (DSM-IV and NINCDS/ADRDA) made or confirmed 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.
6 CT or MRI within the last 36 months consistent with a diagnosis of Alzheimer’s disease without any other clinically significant comorbid pathologies found. A copy of the report will be required and should be appended to the case report form. 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.
7 Prior use of cholinesterase inhibitors (Aricept®, Exelon®, Cognex®, Reminyl/Razadyne®, metrifonate, physostigmine) and memantine is allowed, provided that the medication was discontinued at least 3 months prior to screening and that it was not discontinued for the purpose of enrolling the patient in the study.
8 Functional Assessment Staging (FAST) score >6a.
9 Patients residing in the community, assisted living facilities (ALF)
or skilled nursing homes.
10 The patient must be expected to complete all procedures scheduled during the Screening and Baseline visits including all efficacy parameters. 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. For patients residing in assisted living facilities or skilled nursing homes, the reporting caregiver may be a professional staff member, provided he or she meets the criteria in 8.2.11, and study visits may take
place in the facility if the study site staff finds this preferable to facilitate the smooth conduct of the study.
11 The caregiver must be a constant and reliable informant with a minimum of three days per week direct contact with the patient (for at least 4 hours per day during waking hours). This contact is necessary to ensure accurate reporting of the patient’s behavior.
12 Patients with stable Type I (Insulin-Dependent) or Type II diabetes are eligible provided they are monitored regularly prior to and during the study to ensure adequate glucose control.
13 Clinical laboratory values within normal limits, and within the sponsor’s guidelines, or abnormalities considered not clinically significant by the investigator and sponsor.
14 Patients with controlled hypertension (sitting diastolic BP < 95mmHg and/or sitting systolic BP <160 mmHg), right bundle branch block (complete or partial), and pacemakers may be included in the study.
15 Patients with thyroid disease also may be included in the study provided they are euthyroid and stable on treatment for at least 3 months prior to screening.
16 Patients with a history of seizure disorder are allowed provided that they are on stable treatment for at least 3 months and have not had a seizure within the past 6 months.
17 Patients must be able to swallow tablet medication; no crushing of
tablets is allowed.
18 Patients should be independent in ambulation or ambulatory-aided (i.e., walker, cane, or wheelchair); vision and hearing (eyeglasses and/or hearing aids permissible) should be sufficient forcompliance with testing procedures.
19 Patients must be sufficiently proficient in the language in which the assessments are to be conducted.
|
|
| E.4 | Principal exclusion criteria |
1 Age range: Patients < 50 years.
2 MMSE score of <1 or >12.
3 FAST score of < 6a.
4 CSDD>18
5 Patients with active or clinically significant conditions affecting absorption, distribution or metabolism of the study medication (e.g., inflammatory bowel disease, gastric or duodenal ulcers or severe lactose intolerance).
6 Patients with a known hypersensitivity to piperidine derivatives or cholinesterase inhibitors.
7 Patients without a reliable caregiver (caregiver responsibilities are described in Section 8.2.11), or patients or caregivers who are unwilling or unable to complete any of the outcome measures and fulfill the requirements of this study.
8 Patients with clinically significant obstructive pulmonary disease or asthma, untreated or not controlled by treatment within 3 months prior to screening.
9 Patient’s with recent (< 2 years) hematologic/oncologic disorders
(mild anemia allowed).
10 Evidence of active, clinically significant and unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease.
11 Patients with a current DSM-IV diagnosis of Major Depressive Disorder (MDD) or any current primary psychiatric diagnosis other than Alzheimer’s disease (as per DSM-IV). Patients with CSDD scores >19 will be considered to have MDD and are
excluded.
12 Patients with dementia complicated by other organic disease (DSM 290.30 or 290.11) are excluded; depressive symptoms and delusions are common in Alzheimer’s disease, but patients with severe symptoms so pronounced that they warrant an alternative, concurrent diagnosis, are excluded.
13 Patients with vascular dementia (See Appendix IIIA) or dementia complicated by tertiary syphilis
14 Patients with a known or suspected history of alcoholism or drug abuse (within the past 10 years).
15 Any condition which would make the patient or the caregiver, in the opinion of the investigator, unsuitable for the study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is the Cornell Scale for Depression in Dementia (CSDD), a 19-item clinician-administered instrument that uses information from interviews with a caregiver or nursing staff member and observation of the patient. The CSDD rates mood related signs, behavioural disturbance, physical signs, cyclic functions, and ideational disturbance. Scores range from 0 to 38, with higher scores indicating more severe behavioural pathology. The primary analysis will consist of the combined scores of the Mood-related Signs and Behavioural Disturbance domains (range 0 to 16). Analysis of the total CSDD score will be a secondary analysis.
|
|
| 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 | 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| 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 |
|
| 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
| |
| 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 | 3 |
| 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 | 3 |
Print
