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

NCT00478205 | Completed Phase 3 Results

• 2 other identifiers: E2020-G000-3262006-004888-54
• Study Type: interventional
• Target: 1,467
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease

Keywords

Moderate to Severe Alzheimer's Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline and Week 24

• 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).

  Baseline and Week 24

Secondary Outcomes (2)

• Change From Baseline to Week 24 in ADCS-ADL Total Score

  Baseline and Week 24

• Change From Baseline to Week 24 in MMSE Total Score

  Baseline and Week 24

Study Arms (2)

1

EXPERIMENTAL

Drug: Aricept (donepezil SR 23 mg)

2

EXPERIMENTAL

Drug: Aricept (donepezil IR 10 mg)

Interventions

Aricept (donepezil SR 23 mg) 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.

Also known as: Donepezil hydrochloride

1

Aricept (donepezil IR 10 mg) 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.

Also known as: Donepezil hydrochloride

2

Eligibility Criteria

• Age: 45 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Eisai Inc.: lead
• Eisai Limited: collaborator

Study Sites (1)

MedTrials, Inc.

Hickory, North Carolina, 28601, United States

Location

Related Publications (6)

• 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.

  PMID: 24073978 DERIVED

• 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.

  PMID: 22930699 DERIVED

• 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.

  PMID: 22572767 DERIVED

• 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.

  PMID: 21689411 DERIVED

• 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.

  PMID: 21612646 DERIVED

• 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.

  PMID: 20678673 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Eisai Inc.
• Organization: Eisai Call Center

888-422-4743

Study Officials

• Jane Yardley, Ph.D

  Eisai Limted

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2007
• First Posted: May 24, 2007
• Study Start: June 1, 2007
• Primary Completion: June 1, 2009
• Last Updated: July 11, 2014
• Results First Posted: February 5, 2013

Record last verified: 2013-01

Locations

US (1)