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Alzheimer's DiseasePhase 3NCT00478205

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

A Phase 3 study testing Aricept (donepezil SR 23 mg) and Aricept (donepezil IR 10 mg) in people with Alzheimer's Disease, run by Eisai Inc. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 45 to 90 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
Aricept (donepezil SR 23 mg) and Aricept (donepezil IR 10 mg)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,467 participants
Where
1 siteUnited States
Study dates
Jun 2007to Jun 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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.

Who cannot join

  • 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 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.
  • 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.
  • Patients with dementia complicated by other organic disease or Alzheimer's disease with delirium.
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  • Patients with drug or alcohol abuse or dependence within the past 5 years according to DSM IV criteria.
  • 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).
  • Patients with evidence of clinically significant, active gastrointestinal, renal, hepatic, respiratory, endocrine, or cardiovascular system disease (including history of life-threatening arrhythmias).
  • 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.
  • Known plan for elective surgery during the treatment period that would require general anesthesia and administration of neuromuscular blocking agents.
  • 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.
  • Patients who are unwilling or unable to fulfill the requirements of the study.
  • Known hypersensitivity to acetylcholinesterase inhibitors or memantine.
  • 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.
  • 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.
  • 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.
  • Patients who cannot swallow or who have difficult swallowing whole tablets.
  • Patients with fecal and/or urinary incontinence who are unable to cooperate with routine specimen collection.
  • Caregivers who are unwilling or unable to give informed consent or otherwise to fulfill the requirements of the study.
  • Caregivers who do not meet certain psychometric test criteria.
  • Any condition that would make the caregiver, in the opinion of the Investigator, unsuitable for the study.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • MedTrials, Inc.

    Hickory, North Carolina, 28601

Other trials in United States

About this study

Official title: Double-Blind, Parallel-Group Comparison of 23 mg Donepezil Sustained Release (SR) to 10 mg Donepezil Immediate Release (IR) in Patients With Moderate to Severe Alzheimer's Disease

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.

Read the detailed description

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.

Being tested
Aricept (donepezil SR 23 mg), Aricept (donepezil IR 10 mg)
Keywords
Moderate to Severe Alzheimer's Disease
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aricept (donepezil SR 23 mg)Drug

    Also called Donepezil hydrochloride

    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.

  • Aricept (donepezil IR 10 mg)Drug

    Also called Donepezil hydrochloride

    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.

Study groups in NCT00478205
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Drug: Aricept (donepezil SR 23 mg)
2ExperimentalNot described
Receives: Drug: Aricept (donepezil IR 10 mg)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline to Week 24 in SIB Total Score

    The SIB is an assessment of cognitive dysfunction across nine domains such as memory, language, and orientation. The score ranges from 0 (worst) to 100 (best). This outcome was calculated using the LOCF (last observation carried forward) method.

    Measured: Baseline and Week 24

  2. Overall Change From Baseline in Modified CIBIC+ to Week 24

    The CIBIC+ is a rating scale derived from an interview with the patient and caregiver with an independent rater designed to measure several domains of patient function, such as mental/cognitive state, behavior, and activities of daily living. The scores range from 1 (marked improvement) to 7 (marked worsening).

    Measured: Baseline and Week 24

Secondary outcomes (2)
  1. Change From Baseline to Week 24 in ADCS-ADL Total Score

    The ADCS-ADL (Alzhemier's Disease Cooperative Study-Activities of Daily Living) is a 19-item assessment scale used to measure a patient's basic functional abilities, such as walking, grooming, and bathing.Scores range from 0 to 54, with a higher score indicating greater functional ability.

    Measured: Baseline and Week 24

  2. Change From Baseline to Week 24 in MMSE Total Score

    The MMSE (Mini-Mental State Examination) is a 30-item test that evaluates 5 domains of cognitive function (orientation to time and place, immediate and delayed recall, attention, calculation, and language). The scores range from 0 (most impaired) to 30 (no impaiment).

    Measured: Baseline and Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionJun 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,467 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00478205
Sponsor's protocol ID
E2020-G000-326
Other IDs
2006-004888-54
Status last verified
Jan 2013
First submitted
22 May 2007
Last updated
11 Jul 2014

Publications

  • Schmitt FA, Saxton J, Ferris SH, Mackell J, Sun Y. Evaluation of an 8-item Severe Impairment Battery (SIB-8) vs. the full SIB in moderate to severe Alzheimer's disease patients participating in a donepezil study. Int J Clin Pract. 2013 Oct;67(10):1050-6. doi: 10.1111/ijcp.12188.

    PubMed 24073978
  • Salloway S, Mintzer J, Cummings JL, Geldmacher D, Sun Y, Yardley J, Mackell J. Subgroup analysis of US and non-US patients in a global study of high-dose donepezil (23 mg) in moderate and severe Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2012 Sep;27(6):421-32. doi: 10.1177/1533317512454708.

    PubMed 22930699
  • Doody RS, Geldmacher DS, Farlow MR, Sun Y, Moline M, Mackell J. Efficacy and safety of donepezil 23 mg versus donepezil 10 mg for moderate-to-severe Alzheimer's disease: a subgroup analysis in patients already taking or not taking concomitant memantine. Dement Geriatr Cogn Disord. 2012;33(2-3):164-73. doi: 10.1159/000338236. Epub 2012 May 10.

    PubMed 22572767
  • Ferris SH, Schmitt FA, Saxton J, Richardson S, Mackell J, Sun Y, Xu Y. Analyzing the impact of 23 mg/day donepezil on language dysfunction in moderate to severe Alzheimer's disease. Alzheimers Res Ther. 2011 Jun 20;3(3):22. doi: 10.1186/alzrt84.

    PubMed 21689411
  • Farlow M, Veloso F, Moline M, Yardley J, Brand-Schieber E, Bibbiani F, Zou H, Hsu T, Satlin A. Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer's disease. BMC Neurol. 2011 May 25;11:57. doi: 10.1186/1471-2377-11-57.

    PubMed 21612646
  • Farlow MR, Salloway S, Tariot PN, Yardley J, Moline ML, Wang Q, Brand-Schieber E, Zou H, Hsu T, Satlin A. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized, double-blind study. Clin Ther. 2010 Jul;32(7):1234-51. doi: 10.1016/j.clinthera.2010.06.019.

    PubMed 20678673

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aricept (donepezil SR 23 mg) and Aricept (donepezil IR 10 mg) in people with Alzheimer's Disease, run by Eisai Inc. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline to Week 24 in SIB Total Score (time frame: Baseline and Week 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00478205, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2014.

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