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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1467 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Efficacy and Safety of Aricept in the Treatment of Severe Alzheimer's Disease

NCT00096473

Alzheimer's Disease Dementia

COMPLETED PHASE3

Compare the Efficacy and Safety of Donepezil Hydrochloride 23 mg Treatment With Continuation of Donepezil Hydrochloride 10 mg Treatment in Japanese Subjects With Severe Alzheimer's Disease

NCT01539031

Alzheimer's Type Dementia

COMPLETED PHASE3

A Randomized, Placebo-Controlled Trial to Examine the Efficacy of Oral Donepezil in Subjects With MCI

NCT00483028

Alzheimer's Disease

COMPLETED NA

Safety, Tolerability, and Efficacy of Donepezil (Aricept) in Parkinson' s Disease (PD) Patients With Dementia

NCT01327859

Parkinson's Disease Dementia

COMPLETED PHASE3

A 28-Week Open Label Extension Study Evaluating Safety and Tolerability of Donepezil Hydrochloride in Subjects With Mild Cognitive Impairment

NCT00934375

Mild Cognitive Impairment

COMPLETED PHASE4

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This study consists of a double-blind, double-dummy, parallel-group comparison of 23 mg donepezil SR with the currently marketed donepezil formulation (10 mg donepezil IR) in patients with moderate to severe Alzheimer's disease. Patients must have been taking 10 mg IR (or a bioequivalent generic) for at least 3 months prior to Screening. The study will consist of 24 weeks of daily administration of study medication, with clinic visits at Screening, Baseline, 3 weeks (safety only), 6 weeks, 12 weeks, 18 weeks and 24 weeks or early termination. Patients will receive either 10 mg donepezil IR in combination with the placebo corresponding to 23 mg donepezil SR, or 23 mg donepezil SR in combination with the placebo corresponding to 10 mg donepezil IR.

A total of approximately 1600 patients will be enrolled to obtain complete data from approximately 1200 completed patients (Revised per Amendment 02). During the Baseline visit, patients will be randomized in a 2:1 ratio (23 mg donepezil SR to 10 mg donepezil IR). The study will be performed at approximately 200 global sites (Asia, Oceania, Europe, India, Israel, North America, South Africa, and South America) (Revised per Amendments 01 and 02). An Independent Data Monitoring Committee (IDMC) will be established to review safety aspects of the study and to evaluate the results of a planned interim analysis.

Patients who complete the study may be eligible to undergo evaluation for enrollment into the open-label extension study, E2020-G000-328.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Alzheimer's Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

Group Type EXPERIMENTAL

Aricept (donepezil SR 23 mg)

Intervention Type DRUG

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.

2

Group Type EXPERIMENTAL

Aricept (donepezil IR 10 mg)

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Aricept (donepezil SR 23 mg)

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.

Intervention Type DRUG

Aricept (donepezil IR 10 mg)

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 Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Donepezil hydrochloride Donepezil hydrochloride

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Written informed consent.
2. Patient Age range: Adult patients, 45 to 90 years of age, inclusive.

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.

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

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.

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

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.

Minimum Eligible Age

45 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No