12 week, open-label study to evaluate the effectiveness and safety of donepezil hydrochloride in the US. Approximately 30 sites will be used, approximately 100 patients will be recruited. Patients will be male or female 50 years or older, ambulatory, with a diagnosis of mild to moderate AD as per DSM-IV and NINCDS/ADRDA criteria, with a MMSE score between 10 and 26 (inclusive) at screen. Treatments will be 5 mg (1 tablet) and 10 mg (2 tablets) donepezil hydrochloride per day. Efficacy will be measured by several assessments: FOME, SDMT, NPI and MMSE. Safety will be assessed by evaluation of the patient''''s medical history, physical, vital signs and neurological examinations, clincial laboratory tests, ECG, concomitatn medicatons and adverse event/serious adverse event reporting. Patients who complete the study will be offered an additional 12-week supply of commerical (Aricept) for AD treatment based on the clinical judgement of the investigator.

Condition	Intervention	Phase
Alzheimer''''s Disease	Drug: DONEPEZIL HYDROCHLORIDE	Phase IV

Further study details as provided by Eisai Medical Research Inc:

Primary Outcomes: FOME (Fuld Object Memory Evaluation) is used to test explicit memory (storage and retrieval of information) through the use of a selective reminding procedure.; SDMT (Symbol Digit Modalities Test) is used to measure speed of mental processing/complex attention and concentration functions.; NPI (Neuropsychiatric Inventory) is a 12-item caregiver-based assessment of behavioral disturbances commonly occurring in patients with AD.; MMSE (the Mini-Mental State Examination) is an 11-item scale to measure cognitive status.
Secondary Outcomes: Safety will be assessed by evaluation of the patient''''s medical history, physical vital signs and neurological examinations, clnical laboratory tests, ECG, concomitant medications and adverse event (AE)/serious event (SAE) reporting.

Ages Eligible for Study:  50 Years and above,  Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA

• Patients who self-identify as Hispanic and currently live in the United States.
• Age range: Patients >= 50 years.
• Sex distribution: both men and women. Women must be two (2) years post-menopausal or surgically sterile.
• MMSE scores between 10 and 26 (inclusive).
• Patients must have diagnostic evidence of AD (DSM-IV and NINCDS/ADRDA criteria) either prior to or at the screening visit. Patients with AD who may also have cerebrovascular disease as evidenced by risk factors such as hypertension, diabetes, elevated cholesterol levels, and smoking are also eligible to enroll in the study. In order to be enrolled, such patients’ clinical conditions must be controlled, and it must be the investigator’s opinion that the patient’s primary diagnosis is AD not vascular dementia. The diagnosis of AD must be recorded in the patient’s clinical record prior to the baseline visit.
• CT or MRI within the last 12 months consistent with a diagnosis of AD without any other clinically significant comorbid pathologies found. Patients with vascular changes may be included provided that they do not meet NINDS-AIREN criteria for probable Vascular Dementia (VaD) (see Appendix VII). 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 neurological disease in addition to AD with onset between the time of the last CT or MRI and the screening evaluation, the scan should be repeated during screening.
• All patients must be naïve to Aricept® treatment. Previous use of an approved or unapproved cholinesterase inhibitor (Exelon® , Cognex®, Reminyl®, metrifonate, physostigmine) or memantine is allowed provided that the medication was discontinued at least 3 months prior to screening and that the discontinuation was not done for the purpose of enrolling the patient in this trial.
• Patients must reside in the community (Residence in an assisted living facility is allowed.)
• 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 caregiver must have a minimum of three days per week of direct contact with the patient (for at least 4 hours per day during waking hours).
• The patient must be capable of reliably completing study assessments including all efficacy parameters (MMSE, SDMT, and FOME) and all procedures scheduled during the screening, baseline and all follow-up visits.
• Patients must have clinical laboratory values within normal limits, and within the Eisai (sponsor) guidelines, or abnormalities considered not clinically significant by the investigator and sponsor.
• Patients with stable insulin-dependent diabetes or diabetes stabilized by diet and/or oral hypoglycemic agents are eligible provided they are monitored regularly to ensure adequacy of control. Patients with known diabetes should have an HbA1c of < 8% 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 also may be included in the study provided they are euthyroid and stable on treatment for at least 3 months prior to screening, and the stable treatment is maintained throughout study.
• 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.
• Patients must be able to swallow tablet medication, no crushing of the tablet is allowed.
• Patient must be ambulatory or ambulatory-aided (i.e., walker or cane, or wheelchair). His/her vision and hearing (eyeglasses and/or hearing aid permissible) must be sufficient for compliance with testing procedures.

EXCLUSION CRITERIA

• Age range: Patients < 50 years.
• MMSE score of < 10 or > 26.
• 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).
• Patients with a known hypersensitivity to piperidine derivatives or cholinesterase inhibitors.
• Patients without a reliable caregiver (caregiver responsibilities are described in Section 8.2.9), or patients or caregivers who are unwilling or unable to complete any of the outcome measures and fulfill the requirements of this study.
• Patients who live in a skilled nursing facility (nursing home) or expect to enter nursing home within the next 3 months.
• Patients with clinically significant obstructive pulmonary disease or asthma not controlled with treatment at any time during the previous 3 months.
• Patients with recent (< 2 years) hematological/oncological disorders.
• Evidence of clinically significant, active gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease.
• Patients with a current DSM-lV diagnosis of Major Depressive Disorder (MDD) or any current primary psychiatric diagnosis other than AD (as per DSM-lV).
• Patients with dementia complicated by delirium (DSM 290.30 or 290.11); depression or delusions are common in AD, and patients with severe symptoms so pronounced that they warrant an alternative, concurrent diagnosis, are excluded.
• Patients with a known or suspected history of alcoholism or drug abuse (within the past 5 years).
• Patients with treated vitamin B-12 deficiency who have not been on a stable dose of medication for at least 3 months prior to the study screening visit and who do not have normal serum B-12 levels at screening.
• Patients with treated hypothyroidism that have not been on a stable dose of medication for 3 months prior to screening and who do not have normal serum T-4 and TSH at screening.
• Patients with diabetes mellitus controlled by diet, oral medication, or insulin who do not have an HbAlc of < 8.0% and a random serum glucose value of < 170 mg/dl.
• Patients previously treated with Ariceptâ (donepezil Hydrochloride).
• Any condition which would make the patient or the caregiver, in the opinion of the investigator, unsuitable for the study

Please refer to this study by ClinicalTrials.gov identifier  NCT00230568

Eisai Medical Services      1-888-422-4743 

New Jersey
      Princeton Medical Institute, Princeton,  New Jersey,  08540,  United States

Study chairs or principal investigators

Honglan Li,  Study Director,  Eisai Medical Research Inc   

Study ID Numbers:  E2020-A001-413
Last Updated:  December 8, 2005
Record first received:  September 29, 2005
ClinicalTrials.gov Identifier:  NCT00230568
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-01-10