The Effectiveness And Safety Of Donepezil Hydrochloride (E2020) In Subjects With Mild To Severe Alzheimer's Disease Residing In An Assisted Living Facility
Condition: Mild to Severe Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Donepezil HCl
Intervention description: One 5 mg tablet per day (for the first 6 weeks) with a full glass of water. For the last 6 weeks, one 10mg tablet per day with a full glass of water.
Intervention MeSH terms: Donepezil
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 97.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No

Summary:

      This is a study to determine the effectiveness and safety of donepezil hydrochloride (E2020)
      used to treat residents of assisted living facilities diagnosed with mild, moderate, or
      severe stage Alzheimer's disease.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age range: Subjects > 50 years of age.

          2. Sex distribution: both men and women. Women must be two (2) years post-menopausal or
             surgically sterile. Women of child bearing potential (< 1 year post menopausal) must
             be practicing effective contraception and have a negative ß-hCG at screening (Women
             who are breast feeding are excluded).

          3. MMSE scores between 5 and 24 (inclusive).

          4. Subjects must have diagnostic evidence of possible or probable AD either prior to or
             at the screening visit based on Diagnostic and Statistical Manual of Mental
             Disorders-IV (DSM-IV) and National Institute of Neurological and Communicative
             Disorders and Stroke criteria.

          5. CT or MRI within the last 12 months consistent with a diagnosis of AD without any
             other clinically significant comorbid pathologies found. A copy of the report will be
             required and will be collected. 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.

          6. The caregiver/ informant can be a family member or a professional and must have had
             contact with the subject at least 6 Weeks prior to study entry and spent at minimum 3
             days a Week (10 hours per Week) with the subject. For study visit, the subject can be
             seen at the Assisted Living Facility (ALF) or in the clinic setting of the
             Investigator. At each visit, the caregiver/informant will provide the information for
             completion of the safety and efficacy assessments based on knowledge of and time spent
             with the subject.

          7. Subjects must reside in an ALF.

          8. The subject is expected to complete all procedures scheduled during the screening,
             baseline, interim, and final visits including all efficacy assessments.

          9. Putative non-prescription/prescription cognitive enhancers (e.g. ginkgo, high-dose
             vitamin E, lecithin, estrogen, non-steroidal anti-inflammatory drugs [NSAIDs]) will
             not be excluded but will be discouraged. If a putative cognitive enhancer is present,
             the dosage must have been stable for at least 3 months prior to the screening visit
             and should not change during the course of the study.

         10. Subjects with controlled hypertension (sitting diastolic BP < 95 mmHg), right bundle
             branch block (complete or partial), and pacemakers may be included in the study.

         11. Subjects 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.

         12. Subjects with a history of seizure disorder are allowed provided that they are on
             stable treatment for at least 3 months prior to screening and have not had a seizure
             within the past 6 months.

         13. Subjects must be able to swallow tablet medication -- no crushing of tablet is
             allowed.

         14. Health: independent or ambulatory aided (i.e., walker or cane, to wheelchair); vision
             and hearing (eyeglasses and/or hearing aid permissible) sufficient for compliance with
             testing procedures.

         15. Subjects must be sufficiently proficient in the language in which the assessments are
             to be conducted.

         16. Subjects 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.

        Exclusion Criteria:

          1. Age range: Subjects < 50 years of age.

          2. MMSE score of ≤4 or ≥25.

          3. Subjects 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).

          4. Subjects with a known hypersensitivity to piperidine derivatives or cholinesterase
             inhibitors.

          5. Subjects living in a skilled nursing home or subjects living in an ALF who may be
             moved to a skilled nursing home during the course of the study. Subjects who transfer
             from an ALF to a skilled nursing home during this study will be discontinued.

          6. Subjects who have taken the following medications within the last 3 months prior to
             screening will be not eligible: Aricept, Exelon, Cognex, Razadyne, Metrifonate,
             Namenda or propentofylline.

          7. Subjects without a reliable caregiver/informant or subjects whose caregiver is
             unwilling or unable to complete the outcome measures and fulfill the requirements of
             this study.

          8. Subjects with clinically significant obstructive pulmonary disease or asthma,
             untreated for > 3 months.

          9. Subjects with recent (< 2 years) hematologic/ oncologic disorders, not including mild
             anemia or basal or squamous cell carcinoma of the skin. Subjects with current evidence
             of malignant neoplasm or recurrent or metastatic disease will be excluded.

         10. Evidence of clinically significant, active gastrointestinal, renal, hepatic, endocrine
             or cardiovascular system disease.

         11. Subject 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).

         12. Subjects with dementia complicated by other organic disease (DSM 290.30 or 290.11) are
             excluded; depression or delusions are common in Alzheimer's disease, and subjects with
             severe symptoms so pronounced that they warrant an alternative, concurrent diagnosis,
             are excluded.

         13. Subjects with a known or suspected history of alcoholism or drug abuse (within the
             past 10 years).

         14. Subjects 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 Free T3, Free T4 and
             TSH at screening.

         15. Subjects 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.

         16. Any subject taking a prohibited medication will be excluded.

         17. Any condition which would make the subject or the caregiver, in the opinion of the
             investigator, unsuitable for the study.