Comparison of 23 mg Donepezil Sustained Release (SR) to 10 mg Donepezil Immediate Release (IR) in Patients With Moderate to Severe Alzheimer's Disease

Inclusion Criteria for Patients:

• Written informed consent.
• Patient Age range: Adult patients, 45 to 90 years of age, inclusive.
• The caregiver must separately meet the specified inclusion/exclusion criteria for caregivers.
• Women must be of non-child-bearing potential (>1 year post-menopausal or surgically sterile).
• There must be diagnostic evidence of probable Alzheimer's disease (AD).
• The patient must have been receiving Aricept at a dose of dose of 10 mg IR (or 10 mg dose of generic donepezil bioequivalent to Aricept), for at least 3 months prior to the Screening visit.
• A cranial image is required, with no evidence of focal brain disease that would account for dementia.
• The patient must meet certain psychometric test criteria related to the degree of impairment of cognitive functioning.
• Health: physically healthy and ambulatory or ambulatory-aided (i.e., walker or cane); corrected vision and hearing sufficient for compliance with testing procedures, and able to read prior to disease onset.
• Clinical laboratory values must be within normal limits or, if abnormal, must be judged not clinically significant by the investigator.
• Specified doses of selective serotonin reuptake inhibitors (SSRIs) are allowed in the study if dosage is within approved dose range and stable for 3 months prior to Screening.
• Other medical conditions, such as hypertension and cardiac disease must be well-controlled and the patient maintained on stable doses of medications for 3 months.
• Patients with diabetes mellitus or risk factors for diabetes mellitus may be enrolled in the study provided that the patient's disease is stable and that there have been no recent hospitalizations for diabetes complications.
• Patients whose serum B12 levels at Screening are below the normal range may nonetheless be admitted to the study if they subsequently show normal levels prior to Baseline.
• Patients with hypothyroidism who are on a stable dose of medication for at least 12 weeks prior to Screening, have normal TSH and free T4 at Screening, and are considered euthyroid will be eligible.
• Concomitant Medications: Under specified circumstances, the following medications may be allowed: chronic daily benzodiazepine use, bronchodilator medications for treatment of chronic obstructive pulmonary disease (COPD), and memantine. Certain other additional prescription treatments for AD, such as other cholinesterase inhibitors, must have been discontinued for at least 3 months prior to screening.
• The patient must have a relative/caregiver who supervises the regular taking of the drug at the correct dose and is alert for possible side effects, unless the patient's legal guardian takes on this task.

Inclusion Criteria for Caregivers:

The designated caregiver must be sufficiently familiar with the patient (as determined by the investigator) to provide accurate data. The caregiver must have regular contact with the patient (i.e., an average of 10 or more hours per week), must be able to observe for possible adverse events, and must be able to accompany the patient to all visits.

Exclusion Criteria for Patients:

• Patients are excluded if they are taking (a) no medication for Alzheimer's disease, (b) Aricept or bioequivalent generic donepezil at doses other than 10 mg daily, or 10 mg for less than 3 months before Screening; (c) other medications for Alzheimer's disease, except that memantine, Vitamin E, fish oil, and/or gingko biloba are allowed if doses have been stable for at least 3 months prior to the Screening visit. Patients undergoing any alternative medical techniques, such as acupuncture or acupressure, specifically for the treatment of AD are not eligible
• No caregiver available to meet the inclusion criteria for caregivers.
• Patients who have no measurable blood levels of donepezil in blood samples collected at Screening.
• Patients with neurological disorders that affect cognition or the ability to assess cogn