Comparison of 23 mg Donepezil Sustained Release (SR) to 10 mg Donepezil Immediate Release (IR) in Patients With Moderate to Severe Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Aricept (donepezil SR 23 mg); Aricept (donepezil IR 10 mg)
Intervention description: Patients will receive study medication orally, once daily, for 24 weeks according to a double-dummy design:
23 mg donepezil SR concurrently with placebo identical in appearance to the 10 mg donepezil IR formulation.; Patients will receive study medication orally, once daily, for 24 weeks according to a double-dummy design:
10 mg donepezil IR concurrently with placebo identical in appearance to the 23 mg donepezil SR formulation.
Intervention MeSH terms: Donepezil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1467.0
Sex: All
Minimum age: 45 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Moderate to Severe Alzheimer's Disease

Summary:

      The purpose of this study is to compare 23 mg donepezil sustained release (SR) to the
      currently marketed formulation of 10 mg donepezil immediate release (IR) in patients with
      moderate to severe Alzheimer's disease.
    

Eligibility criteria:

        Inclusion Criteria for Patients:

          1. Written informed consent.

          2. Patient Age range: Adult patients, 45 to 90 years of age, inclusive.

          3. The caregiver must separately meet the specified inclusion/exclusion criteria for
             caregivers.

          4. Women must be of non-child-bearing potential (>1 year post-menopausal or surgically
             sterile).

          5. There must be diagnostic evidence of probable Alzheimer's disease (AD).

          6. 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.

          7. A cranial image is required, with no evidence of focal brain disease that would
             account for dementia.

          8. The patient must meet certain psychometric test criteria related to the degree of
             impairment of cognitive functioning.

          9. 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.

         10. Clinical laboratory values must be within normal limits or, if abnormal, must be
             judged not clinically significant by the investigator.

         11. 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.

         12. 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.

         13. 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.

         14. 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.

         15. 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.

         16. 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.

         17. 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:

          1. 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

          2. No caregiver available to meet the inclusion criteria for caregivers.

          3. Patients who have no measurable blood levels of donepezil in blood samples collected
             at Screening.

          4. Patients with neurological disorders that affect cognition or the ability to assess
             cognition but are distinguishable from Alzheimer's disease. These include, but are not
             limited to, Parkinson's disease, multi-infarct dementia, and dementia due to
             cerebrovascular disease.

          5. Patients with psychiatric disorders affecting the ability to assess cognition such as
             schizophrenia, bipolar or unipolar depression. Patients with clinically significant
             sleep disorders will also be excluded unless these are controlled by treatment and
             clinically stable for > 3 months prior to screening.

          6. Patients with dementia complicated by other organic disease or Alzheimer's disease
             with delirium.

          7. Patients with drug or alcohol abuse or dependence within the past 5 years according to
             DSM IV criteria.

          8. Patients with any conditions affecting absorption, distribution, or metabolism of the
             study medication (e.g., inflammatory bowel disease, gastric or duodenal ulcers,
             hepatic disease, or severe lactose intolerance).

          9. Patients with evidence of clinically significant, active gastrointestinal, renal,
             hepatic, respiratory, endocrine, or cardiovascular system disease (including history
             of life-threatening arrhythmias).

         10. Patients with a history of cancer (does not include basal or squamous cell carcinoma
             of the skin) treated within 5 years prior to study entry, or current evidence of
             malignant neoplasm, recurrent, metastatic disease. Males with localized prostate
             cancer requiring no treatment would not be excluded.

         11. Known plan for elective surgery during the treatment period that would require general
             anesthesia and administration of neuromuscular blocking agents.

         12. Donation of blood or blood products during 30 days prior to Screening or plans to
             donate blood while participating in the study or within 30 days after completion of
             the study.

         13. Patients who are unwilling or unable to fulfill the requirements of the study.

         14. Known hypersensitivity to acetylcholinesterase inhibitors or memantine.

         15. Use of any prohibited prior or concomitant medications) Any condition that would make
             the patient, in the opinion of the investigator, unsuitable for the study.

         16. Involvement in any other investigational drug clinical trial during the preceding 3
             months, or likely involvement in any other such trial during the course of this study.

         17. Patients taking concomitant antidepressant medication known to have significant
             anticholinergic effects, such as tricyclic antidepressants prescribed at doses
             recommended for the treatment of major depression.

         18. Patients who cannot swallow or who have difficult swallowing whole tablets.

         19. Patients with fecal and/or urinary incontinence who are unable to cooperate with
             routine specimen collection.

        Exclusion Criteria for Caregivers:

          1. Caregivers who are unwilling or unable to give informed consent or otherwise to
             fulfill the requirements of the study.

          2. Caregivers who do not meet certain psychometric test criteria.

          3. Any condition that would make the caregiver, in the opinion of the Investigator,
             unsuitable for the study.